肝局灶性结节性增生、肝细胞腺瘤及肝细胞癌中微卫星杂合性丢失研究
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摘要
目的：
肝细胞腺瘤(HCA)和局灶性结节性增生(FNH)是发生于结构正常或基本正常肝脏的良性病变。已经知道前者是一种肿瘤性病变,具有特征性的分子病理学改变,而后者的性质及发病机制尚未被阐明。本研究选取多个与HCC发生有关联的微卫星标志,以期能够揭示FNH和HCA中的染色体等位基因杂合性丢失(LOH)在肝肿瘤发生、发展中的作用。
方法：
选取5例经典型FNH,9例HCA和18例分化好的(Edmondson I或Ⅱ级)肝细胞肝癌(HCC),通过聚合酶链式反应(PCR)扩增57个微卫星位点,应用变性聚丙烯酰胺凝胶电泳显示LOH。通过免疫组织化学方法对9例肝腺瘤检测β-catenin蛋白表达。
结果：
18例HCC均为乙型肝炎病毒感染,其中一例同时合并丙型肝炎病毒感染。所有HCC标本中均可检测LOH,单一病例发生LOH的微卫星均数为4个(0-12)。57个检测的位点中,33个(58%)被累及,6个在这些HCC标本中呈现高频(≥30%)LOH,位于6q、8p、11p、16q和17p。
9例HCA中,2例伴有不典型增生(即小细胞性改变,SCC),β-catenin免疫组织化学检测均显示胞膜阳性,未见明确胞浆和胞核阳性。9例HCA均显示有等位基因失衡,累及16个(28%)位点,其中8个为高频位点,位于11p、13q和17p。单个HCA病变发生LOH位点均数为3个(1-5)。
5例FNH中均未检测到SCC改变,LOH检测均为阴性。然而,这些FNH标本中都可以见到多个透明细胞为主型的变异肝细胞病灶(FAH)和结节(NAH),后一种病变构成FNH中多数体积较大(直径>1 mm)的小结节。选取NAH较多且明显的1例FNH病变,应用显微切割分离了25个NAH,其中13个病变多数微卫星位点扩增成功。这些NAH病变均显示出LOH,共累及21个(37%)位点,其中6个为高频位点,位于8p、11p、13q和17p。单个病变发生LOH的位点均数为4个(1-6)。不同NAH病变之间LOH组型也不相同,显示是互相独立的病变个体。
NAH、HCA和HCC的LOH位点分布不同,频率最高的位点分别是D8S298(70%)、D11S1301 (75%)和D6S1008 (50%)。这三种病变中,NAH中发生LOH的位点累及染色体区域与HCA基本相似。然而,前者中8p发生LOH的频度高于后者；NAH与HCA在16q改变中也不相同,前者累及7个位点中的5个,后者仅累及1个。
结论：
分化较好的HCC中存在广泛的等位基因失平衡,高频率LOH位点定位于染色体6q、8p、11p、16q和17p；HCA中也存在LOH,但分布较为局限,高频位点位于11p、13q和17p。FNH中未检测到LOH,与其多克隆特征一致,但组织学检查发现广泛存在FAH和NAH。对显微切割的不同NAH微卫星位点检测显示,所有小结节均存在LOH,提示他们都已经属于肿瘤性病变；NAH中LOH高频位点位于8p、11p、13q和17p,与HCA相似。来自同一FNH的不同NAH病变具有不同的LOH组型,显示它们相互独立。这组数据提示,经典FNH中小结节状的组织学改变实际上反映了多个NAH的成簇发生。
Objective:
Hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) are benign focal lesions occuring in normal or nearly normal liver. HCA has been found to be neoplastic, characterized by alterations in a few molecular pathways. The clonality status of FNH remains to be clarified, and its pathogenesis is largely unknown. In the current study, a comprehensive observation was carried out on FNH and HCA for loss of heterrozygosity (LOH) using 57 microsatellite markers, where allelic imbalances had been associated to HCC development. Possible roles of the genetic alterations in hepatotocarcinogenesis were evaluated
Methods:
5 classical FNH lesions,9 HCAs and 18 well-differentiated HCCs (Edmondson grade I or II) were used in this study. A total number of 57 microsatellite markers were examined. The sequences were amplified through polymerase-chain reaction, and LOH were visualized on denatured polyacrylamide gels by silver staining. Expression of P-catenin was assessd in 9 HCAs by immunohistochemistry.
Results:
All of the 18 HCCs were found in livers with chroni hepatitis B and cirrhosis, with coinfection of hepatitis C virus found in one of the cases. LOH was demonstrated in all of the HCCs examined. Numbers of loci revealed in each case ranged from 0 to 12, with their average being 4. Among the 57 loci,33 (58%) showed allelic imbalances in HCCs, with highly frequent (≥30%) LOH detected in 6 loci located on 6q,8p, 11p,16q and 17p.
Liver cell dysplasia (small-cell change, SCC) was observed in 2 out of 9 HCAs examined. A memebranous, rather than cytoplasmic or nuclear, immunoreactivity was demonstrated in all of the HCA. LOH was also detected in these lesions. Numbers of loci with LOH in each HCA lesion ranged from 1 to 5, with their average being 3. Sixteen loci (28%) were affected, with 8, on 11p,13q and 17p, showing highly frequent imbalances.
LOH was not found in the 5 FNH lesions as detected as a whole. However, foci of altered hepatocytes (FAH) and nodules of altered hepatocytes (NAH) composed mainly of clear cells were identified in these lesions. NAH were found to occupy majority of the larger nodules, sizing>1 mm in diameter, within FNH. NAH were microdissected from an FNH lesion showing many well-circumscribed larger nodules. A total number of 25, NAH were obtained, and amplification was successful for most of the 57 loci in 13 of them. Numbers of loci ranged from one to 6, with their average being 4. Twenty-one loci (37%) were affected, with 6, located on 8p, 11p,13q and 17p, showing highly frequent LOH.
NAH, HCA and HCC were found to be different in their LOH profiles, with LOH detected in highest frequencies at the loci D8S298 (70%), D11S1301 (75%) and D6S1008 (50%), respectively. Distribution pattern of LOH in NAH was largely similar to that in HCA. However,8p was affected more frequently in the former than in the latter lesion. In addition, they were also shown to be different in the 16q alterations, with 5 of the 7 loci affected in NAH and only one in HCA.
Conclusions:
Allelic imbalances were found in well-differentiated HCC, with highly frequent LOH detected on chromosomal arms 6q,8p, 11p,16q and 17p. LOH was also identified in HCA, but it affected fewer loci than in HCC samples, detected in high frequencies at the loci on 11p, 13q and 17p. No LOH was found in whole FNH lesions, which is in agreement with its polyclonality as demonstrated previously. However, frequent occurrences of FAH and NAH were demonstrated within the lesions. The microsatellite sequences from the microdissected NAH were also examined. LOH was detected in all of the lesions at lest at one locus, indicating their monoclonalality. Chromosomal arms 8p, 11p,13q and 17p were affected in NAH in high frequencies, the distribution pattern being largely similar to HCA. Different LOH profiles were found in different NAH, indicating that they developed independently. These data hint that the nodular pattern characterized by classical FNH may reflect the clustered occurrence within the lesion.
肝细胞腺瘤(HCA)和局灶性结节性增生(FNH)是发生于结构正常或基本正常肝脏的良性病变。已经知道前者是一种肿瘤性病变,具有特征性的分子病理学改变,而后者的性质及发病机制尚未被阐明。本研究选取多个与HCC发生有关联的微卫星标志,以期能够揭示FNH和HCA中的染色体等位基因杂合性丢失(LOH)在肝肿瘤发生、发展中的作用。
方法：
选取5例经典型FNH,9例HCA和18例分化好的(Edmondson I或Ⅱ级)肝细胞肝癌(HCC),通过聚合酶链式反应(PCR)扩增57个微卫星位点,应用变性聚丙烯酰胺凝胶电泳显示LOH。通过免疫组织化学方法对9例肝腺瘤检测β-catenin蛋白表达。
结果：
18例HCC均为乙型肝炎病毒感染,其中一例同时合并丙型肝炎病毒感染。所有HCC标本中均可检测LOH,单一病例发生LOH的微卫星均数为4个(0-12)。57个检测的位点中,33个(58%)被累及,6个在这些HCC标本中呈现高频(≥30%)LOH,位于6q、8p、11p、16q和17p。
9例HCA中,2例伴有不典型增生(即小细胞性改变,SCC),β-catenin免疫组织化学检测均显示胞膜阳性,未见明确胞浆和胞核阳性。9例HCA均显示有等位基因失衡,累及16个(28%)位点,其中8个为高频位点,位于11p、13q和17p。单个HCA病变发生LOH位点均数为3个(1-5)。
5例FNH中均未检测到SCC改变,LOH检测均为阴性。然而,这些FNH标本中都可以见到多个透明细胞为主型的变异肝细胞病灶(FAH)和结节(NAH),后一种病变构成FNH中多数体积较大(直径>1 mm)的小结节。选取NAH较多且明显的1例FNH病变,应用显微切割分离了25个NAH,其中13个病变多数微卫星位点扩增成功。这些NAH病变均显示出LOH,共累及21个(37%)位点,其中6个为高频位点,位于8p、11p、13q和17p。单个病变发生LOH的位点均数为4个(1-6)。不同NAH病变之间LOH组型也不相同,显示是互相独立的病变个体。
NAH、HCA和HCC的LOH位点分布不同,频率最高的位点分别是D8S298(70%)、D11S1301 (75%)和D6S1008 (50%)。这三种病变中,NAH中发生LOH的位点累及染色体区域与HCA基本相似。然而,前者中8p发生LOH的频度高于后者；NAH与HCA在16q改变中也不相同,前者累及7个位点中的5个,后者仅累及1个。
结论：
分化较好的HCC中存在广泛的等位基因失平衡,高频率LOH位点定位于染色体6q、8p、11p、16q和17p；HCA中也存在LOH,但分布较为局限,高频位点位于11p、13q和17p。FNH中未检测到LOH,与其多克隆特征一致,但组织学检查发现广泛存在FAH和NAH。对显微切割的不同NAH微卫星位点检测显示,所有小结节均存在LOH,提示他们都已经属于肿瘤性病变；NAH中LOH高频位点位于8p、11p、13q和17p,与HCA相似。来自同一FNH的不同NAH病变具有不同的LOH组型,显示它们相互独立。这组数据提示,经典FNH中小结节状的组织学改变实际上反映了多个NAH的成簇发生。
Objective:
Hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) are benign focal lesions occuring in normal or nearly normal liver. HCA has been found to be neoplastic, characterized by alterations in a few molecular pathways. The clonality status of FNH remains to be clarified, and its pathogenesis is largely unknown. In the current study, a comprehensive observation was carried out on FNH and HCA for loss of heterrozygosity (LOH) using 57 microsatellite markers, where allelic imbalances had been associated to HCC development. Possible roles of the genetic alterations in hepatotocarcinogenesis were evaluated
Methods:
5 classical FNH lesions,9 HCAs and 18 well-differentiated HCCs (Edmondson grade I or II) were used in this study. A total number of 57 microsatellite markers were examined. The sequences were amplified through polymerase-chain reaction, and LOH were visualized on denatured polyacrylamide gels by silver staining. Expression of P-catenin was assessd in 9 HCAs by immunohistochemistry.
Results:
All of the 18 HCCs were found in livers with chroni hepatitis B and cirrhosis, with coinfection of hepatitis C virus found in one of the cases. LOH was demonstrated in all of the HCCs examined. Numbers of loci revealed in each case ranged from 0 to 12, with their average being 4. Among the 57 loci,33 (58%) showed allelic imbalances in HCCs, with highly frequent (≥30%) LOH detected in 6 loci located on 6q,8p, 11p,16q and 17p.
Liver cell dysplasia (small-cell change, SCC) was observed in 2 out of 9 HCAs examined. A memebranous, rather than cytoplasmic or nuclear, immunoreactivity was demonstrated in all of the HCA. LOH was also detected in these lesions. Numbers of loci with LOH in each HCA lesion ranged from 1 to 5, with their average being 3. Sixteen loci (28%) were affected, with 8, on 11p,13q and 17p, showing highly frequent imbalances.
LOH was not found in the 5 FNH lesions as detected as a whole. However, foci of altered hepatocytes (FAH) and nodules of altered hepatocytes (NAH) composed mainly of clear cells were identified in these lesions. NAH were found to occupy majority of the larger nodules, sizing>1 mm in diameter, within FNH. NAH were microdissected from an FNH lesion showing many well-circumscribed larger nodules. A total number of 25, NAH were obtained, and amplification was successful for most of the 57 loci in 13 of them. Numbers of loci ranged from one to 6, with their average being 4. Twenty-one loci (37%) were affected, with 6, located on 8p, 11p,13q and 17p, showing highly frequent LOH.
NAH, HCA and HCC were found to be different in their LOH profiles, with LOH detected in highest frequencies at the loci D8S298 (70%), D11S1301 (75%) and D6S1008 (50%), respectively. Distribution pattern of LOH in NAH was largely similar to that in HCA. However,8p was affected more frequently in the former than in the latter lesion. In addition, they were also shown to be different in the 16q alterations, with 5 of the 7 loci affected in NAH and only one in HCA.
Conclusions:
Allelic imbalances were found in well-differentiated HCC, with highly frequent LOH detected on chromosomal arms 6q,8p, 11p,16q and 17p. LOH was also identified in HCA, but it affected fewer loci than in HCC samples, detected in high frequencies at the loci on 11p, 13q and 17p. No LOH was found in whole FNH lesions, which is in agreement with its polyclonality as demonstrated previously. However, frequent occurrences of FAH and NAH were demonstrated within the lesions. The microsatellite sequences from the microdissected NAH were also examined. LOH was detected in all of the lesions at lest at one locus, indicating their monoclonalality. Chromosomal arms 8p, 11p,13q and 17p were affected in NAH in high frequencies, the distribution pattern being largely similar to HCA. Different LOH profiles were found in different NAH, indicating that they developed independently. These data hint that the nodular pattern characterized by classical FNH may reflect the clustered occurrence within the lesion.
引文
1. Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S et al: Genotype-phenotype correlation in hepatocellular adenoma:new classification and relationship with HCC. Hepatology 2006,43(3):515-524.
2. Reddy KR, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D, Badalamenti S, Jeffers L, Tzakis A, Schiff ER:Benign and solid tumors of the liver:relationship to sex, age, size of tumors, and outcome. The American surgeon 2001,67(2):173-178.
3. Knowles DM,2nd, Casarella WJ, Johnson PM, Wolff M:The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Medicine 1978,57(3):223-237.
4. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
5. Bannasch P, Schroder CH:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
6. Chen YW, Jeng YM, Yeh SH, Chen PJ:P53 gene and Wnt signaling in benign neoplasms:beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia. Hepatology 2002,36(4 Pt 1):927-935.
7. Ishak KG AP, Sobin LH:Definition and explanatory notes:liver. In:Ishak KG, Anthony PR, Sobin LH, eds. Histological typing of tumors of the liver. International Histological Classification of Tumors Berlin:WHO,1994:9-36.
8. Wanless IR, Mawdsley C, Adams R:On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology (Baltimore, Md 1985,5(6):1194-1200.
9. Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C:Focal nodular hyperplasia of the liver:a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. The American journal of surgical pathology 1999, 23(12):1441-1454.
10. Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P:Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology (Baltimore, Md 1997,26(4):891-895.
11. Gaffey Mj Fau-Iezzoni JC, Iezzoni Jc Fau-Weiss LM, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 1996,148(4):1089-1096.
12. Paradis V, Benzekri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, Belghiti J, Vidaud M, Degott C, Bedossa P:Telangiectatic focal nodular hyperplasia:a variant of hepatocellular adenoma. Gastroenterology 2004,126(5):1323-1329.
13. Nakayama S, Kanbara Y, Nishimura T, Nishida N, Hanioka K, Morita M, Fujita M, Sakurai K, Hayashi Y:Genome-wide microsatellite analysis of focal nodular hyperplasia:a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma. Journal of hepato-biliary-pancreatic surgery 2006, 13(5):416-420.
14. Chen YJ, Chen PJ, Lee MC, Yeh SH, Hsu MT, Lin CH:Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. Genes, chromosomes & cancer 2002,35(2):138-143.
15. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
16. Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
17. 巩丽,张宏图,张伟,李爱宁,刘杉,孙耘田,刘贵秋,苏勤：克隆性分析技术在肝脏局灶性结节性增生诊断中的应用.世界华人消化杂志 2006,14(6)：568-575.
18. Zhang SH, Cong WM, Wu MC:Focal nodular hyperplasia with concomitant hepatocellular carcinoma:a case report and clonal analysis. Journal of clinical pathology 2004,57(5):556-559.
19. Chen TC, Chou TB, Ng KF, Hsieh LL, Chou YH:Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis. Virchows Arch 2001,438(4):408-411.
20. Kellner U, Jacobsen A, Kellner A, Mantke R, Roessner A, Rocken C:Comparative genomic hybridization. Synchronous occurrence of focal nodular hyperplasia and hepatocellular carcinoma in the same liver is not based on common chromosomal aberrations. American journal of clinical pathology 2003,119(2):265-271.
21. 苏勤：人肝细胞癌的癌前期病变.诊断病理学杂志2003,10：112-115.
22. 初霞,苏勤,巩丽,张伟,王淑芳,朱少君,李爱宁,冯英明：慢性乙型肝炎和
肝硬化组织中变异肝细胞结节的克隆性.世界华人消化杂志 2005,13(8)：945-952.
23. Edmondson HA, Steiner PE:Primary carcinoma of the liver:a study of 100 cases among 48,900 necropsies. Cancer 1954,7(3):462-503.
24. 苏勤,刘彦仿：乙型肝炎、肝硬变中癌前病变的形态学和免疫组织化学观察.第四军医大学学报1995,16(2)：85-88.
25. Nesbitt MN:Chimeras vs X inactivation mosaics:significance of differences in pigment distribution. Developmental biology 1974,38(1):202-207.
26. Ochiai T, Ueda K, Urata Y, Yamano T, Konishi E, Ogino A, Kawai K, Itoi H, Sonoyama T, Yamagishi H et al: [Clonal analysis of hepatocellular carcinoma]. Gan to kagaku ryoho 1996,23 Suppl 2:182-188.
27. Nagai H, Pineau P, Tiollais P, Buendia MA, Dejean A:Comprehensive allelotyping of human hepatocellular carcinoma. Oncogene 1997,14(24):2927-2933.
28. Sun M, Eshleman JR, Ferrell LD, Jacobs G, Sudilovsky EC, Tuthill R, Hussein MR, Sudilovsky O:An early lesion in hepatic carcinogenesis:loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region. Hepatology (Baltimore, Md 2001,33(6):1415-1424.
29. Maggioni M, Coggi G, Cassani B, Bianchi P, Romagnoli S, Mandelli A, Borzio M, Colombo P, Roncalli M:Molecular changes in hepatocellular dysplastic nodules on microdissected liver biopsies. Hepatology 2000,32(5):942-946.
30. Kondo Y, Kanai Y, Sakamoto M, Mizokami M, Ueda R, Hirohashi S:Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology 2000,32(5):970-979.
31. Zhang SH, Cong WM, Xian ZH, Wu MC:Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China. World J Gastroenterol 2005,11(20):3034-3039.
32. Kahng YS, Lee YS, Kim BK, Park WS, Lee JY, Kang CS:Loss of heterozygosity of chromosome 8p and 11p in the dysplastic nodule and hepatocellular carcinoma. Journal of gastroenterology and hepatology 2003,18(4):430-436.
33. Kim H, Lee MJ, Kim MR, Chung IP, Kim YM, Lee JY, Jang JJ:Expression of cyclin D1, cyclin E, cdk4 and loss of heterozygosity of 8p,13q,17p in hepatocellular carcinoma:comparison study of childhood and adult hepatocellular carcinoma. Liver 2000,20(2):173-178.
34. Chan KL, Lee JM, Guan XY, Fan ST, Ng IO:High-density allelotyping of chromosome 8p in hepato cellular carcinoma and clinicopathologic correlation. Cancer 2002,94(12):3179-3185.
35. Sheu JC, Lin YW, Chou HC, Huang GT, Lee HS, Lin YH, Huang SY, Chen CH, Wang JT, Lee PH et al:Loss of heterozygosity and microsatellite instability in hepato cellular carcinoma in Taiwan. British journal of cancer 1999,80(3-4):468-476.
36. Wong CM, Lee JM, Ching YP, Jin DY, Ng IO:Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer research 2003,63(22):7646-7651.
37. Dore MP, Realdi G, Mura D, Onida A, Massarelli G, Dettori G, Graham DY, Sepulveda AR:Genomic instability in chronic viral hepatitis and hepatocellular carcinoma. Human pathology 2001,32(7):698-703.
38. Henegariu O, Heerema NA, Dlouhy SR, Vance GH, Vogt PH:Multiplex PCR:critical parameters and step-by-step protocol. BioTechniques 1997,23(3):504-511.
39. Piao Z, Park C, Park JH, Kim H:Allelotype analysis of hepatocellular carcinoma. International journal of cancer 1998,75(1):29-33.
40. Wong CM, Lee JM, Lau TC, Fan ST, Ng IO:Clinicopathological significance of loss of heterozygosity on chromosome 13q in hepatocellular carcinoma. Clin Cancer Res 2002,8(7):2266-2272.
41. Maruyama K, Ochiai A, Akimoto S, Nakamura S, Baba S, Moriya Y, Hirohashi S: Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human co lorectal cancer. Oncology 2000,59(4):302-309.
42. Bosch FX, Ribes J, Borras J:Epidemiology of primary liver cancer. Seminars in liver disease 1999,19(3):271-285.
43. Edmondson HA:Tumors of the liver and intrahepatic bile ducts. In:Atlas of tumor pathology. Washington (DC):Armed Forces Institute of Pathology; 1958.
44. Scalori A, Tavani A, Gallus S, La Vecchia C, Colombo M:Oral contraceptives and the risk of focal nodular hyperplasia of the liver:a case-control study. American journal of obstetrics and gynecology 2002,186(2):195-197.
45. Mathieu D, Kobeiter H, Cherqui D, Rahmouni A, Dhumeaux D:Oral contraceptive intake in women with focal nodular hyperplasia of the liver. Lancet 1998, 352(9141):1679-1680.
46. Makhlouf HR, Abdul-Al HM, Goodman ZD:Diagnosis of focal nodular hyperplasia of the liver by needle biopsy. Human pathology 2005,36(11):1210-1216.
47. Bioulac-Sage P, Balabaud C, Bedossa P, Scoazec JY, Chiche L, Dhillon AP, Ferrell L, Paradis V, Roskams T, Vilgrain V et al:Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia:Bordeaux update. Journal of hepatology 2007, 46(3):521-527.
48. Gaiani S, Piscaglia F, Serra C, Bolondi L:Hemodynamics in focal nodular hyperplasia. Journal of hepatology 1999,31(3):576.
49. Fukukura Y, Nakashima O, Kusaba A, Kage M, Kojiro M:Angioarchitecture and blood circulation in focal nodular hyperplasia of the liver. Journal of hepatology 1998, 29(3):470-475.
50. Vecchio FM, Fabiano A, Ghirlanda G, Manna R, Massi G:Fibrolamellar carcinoma of the liver:the malignant counterpart of focal nodular hyperplasia with oncocytic change. American journal of clinical pathology 1984,81(4):521-526.
51. Gaffey MJ, Iezzoni JC, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. The American journal of pathology 1996,148(4):1089-1096.
52. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31 (1):126-133.
53. Farber E, Sarma DS:Hepatocarcinogenesis:a dynamic cellular perspective. Laboratory investigation; a journal of technical methods and pathology 1987, 56(1):4-22.
54. Field D, Wills C:Long, polymorphic microsatellites in simple organisms. Proceedings 1996,263(1367):209-215.
55. Hancock JM:The contribution of slippage-like processes to genome evolution. Journal of molecular evolution 1995,41(6):1038-1047.
56. 张建军,安倩：微卫星与肿瘤.癌症2000,19(10)：948-950.
57. Stallings RL:Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence:implications for human genetic diseases. Genomics 1994,21(1):116-121.
58. Lyon MF:X-chromosome inactivation and developmental patterns in mammals. Biological reviews of the Cambridge Philosophical Society 1972,47(1):1-35.
59. Gilliland DG, Blanchard KL, Levy J, Perrin S, Bunn HF:Clonality in myeloproliferative disorders:analysis by means of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 1991,88(15):6848-6852.
60. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW:Methylation of HpaⅡ and HhaⅠ sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. American journal of human genetics 1992,51 (6):1229-1239.
61. Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S et al: Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype. Cancer research 1997,57(10):1986-1990.
62. 方嬿,李国辉,卓子兰：20例原发性肝癌实体瘤的细胞遗传学研究.中国优生与遗传杂志1996,4：34-37.
63. 王辉云,关新元,方嬿：肝癌染色体DNA拷贝数的变化及其与临床病理和预后的关系.癌症1999,18：509-513.
64. Schleiermacher G, Delattre O, Peter M, Mosseri V, Delonlay P, Vielh P, Thomas G, Zucker JM, Magdelenat H, Michon J:Clinical relevance of loss heterozygosity of the short arm of chromosome 1 in neuroblastoma:a single-institution study. International journal of cancer 1996,69(2):73-78.
65. Bieche I, Champeme MH, Matifas F, Cropp CS, Callahan R, Lidereau R:Two distinct regions involved in lp deletion in human primary breast cancer. Cancer research 1993, 53(9):1990-1994.
66. Yeh SH, Chen PJ, Chen HL, Lai MY, Wang CC, Chen DS:Frequent genetic alterations at the distal region of chromosome lp in human hepatocellular carcinomas. Cancer research 1994,54(15):4188-4192.
67. Kraus JA, Albrecht S, Wiestler OD, von Schweinitz D, Pietsch T:Loss of heterozygosity on chromosome 1 in human hepatoblastoma. International journal of cancer 1996,67(4):467-471.
68. Becker SA, Zhou YZ, Slagle BL:Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer research 1996, 56(21):5092-5097.
69. Steinemann D, Skawran B, Becker T, Tauscher M, Weigmann A, Wingen L, Tauscher S, Hinrichsen T, Hertz S, Flemming P et al: Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization. Clin Gastroenterol Hepatol 2006,4(10):1283-1291.
70. Piao Z, Kim NG, Kim H, Park C:Deletion mapping on the short arm of chromosome 8 in hepatocellular carcinoma. Cancer letters 1999,138(1-2):227-232.
71. Liao C, Zhao M, Song H, Uchida K, Yokoyama KK, Li T:Identification of the gene for a novel liver-related putative tumor suppressor at a high-frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma. Hepatology 2000,32(4 Pt 1):721-727.
72. Fujiwara Y, Ohata H, Kuroki T, Koyama K, Tsuchiya E, Monden M, Nakamura Y: Isolation of a candidate tumor suppressor gene on chromosome 8p21.3-p22 that is homologous to an extracellular domain of the PDGF receptor beta gene. Oncogene 1995,10(5):891-895.
73. Aaronson SA:Growth factors and cancer. Science 1991,254(5035):1146-1153.
74. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC:Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer research 1998, 58(10):2196-2199.
75. Durkin ME, Yuan BZ, Thorgeirsson SS, Popescu NC:Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7). Gene 2002, 288(1-2):119-127.
76. Rogler CE, Sherman M, Su CY, Shafritz DA, Summers J, Shows TB, Henderson A, Kew M:Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science (New York,NY1985,230(4723):319-322.
77. Liu H, Ling Y, Gong Y, Sun Y, Hou L, Zhang B:DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation. Molecular and cellular biochemistry 2007,300(1-2):249-258.
78. Kuroki T, Fujiwara Y, Nakamori S, Imaoka S, Kanematsu T, Nakamura Y:Evidence for the presence of two tumour-suppressor genes for hepatocellular carcinoma on chromosome 13q. British journal of cancer 1995,72(2):383-385.
79. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986,323(6089):643-646.
80. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G:Identification of the breast cancer susceptibility gene BRCA2. Nature 1995,378(6559):789-792.
81. Tsukamoto K, Ito N, Yoshimoto M, Iwase T, Tada T, Kasumi F, Nakamura Y, Emi M: Two distinct commonly deleted regions on chromosome 13q suggest involvement of BRCA2 and retinoblastoma genes in sporadic breast carcinomas. Cancer 1996, 78(9):1929-1934.
82. Grimmond SM, Palmer JM, Walters MK, Scott C, Nancarrow DJ, Teh BT, Elmes C, Pyke C, Khoo SK, Bennett I et al: Confirmation of susceptibility locus on chromosome 13 in Australian breast cancer families. Human genetics 1996, 98(1):80-85.
83. 邵建永,李晓明,刘宗石,林汉良：原发性肝癌患者17号和16号染色体等位基因杂合性丢失的研究.中华医学杂志1999,79(6)：428-430.
84. Tsuda H, Zhang WD, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S:Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America 1990,87(17):6791-6794.
85. Yeh SH, Chen PJ, Lai MY, Chen DS:Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma:association with elevated alpha-fetoprotein production. Gastroenterology 1996,110(1):184-192.
86. Fujimoto Y, Hampton LL, Wirth PJ, Wang NJ, Xie JP, Thorgeirsson SS:Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. Cancer research 1994,54(1):281-285.
87. Marchio A, Meddeb M, Pineau P, Danglot G, Tiollais P, Bernheim A, Dejean A: Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes, chromosomes & cancer 1997, 18(1):59-65.
88. Zhao X, Li J, He Y, Lan F, Fu L, Guo J, Zhao R, Ye Y, He M, Chong W et al: A novel growth suppressor gene on chromosome 17p13.3 with a high frequency of mutation in human hepatocellular carcinoma. Cancer research 2001,61(20):7383-7387.
89. Kochetkova M, McKenzie OL, Bais AJ, Martin JM, Secker GA, Seshadri R, Powell JA, Hinze SJ, Gardner AE, Spendlove HE et al: CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3. Cancer research 2002,62(16):4599-4604.
90. Kumar R, Neilsen PM, Crawford J, McKirdy R, Lee J, Powell JA, Saif Z, Martin JM, Lombaerts M, Cornelisse CJ et al: FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex. Cancer research 2005,65(24):11304-11313.
91. Francke U, Darras BT, Zander NF, Kilimann MW:Assignment of human genes for
phosphorylase kinase subunits alpha (PHKA) to Xq12-q13 and beta (PHKB) to 16q12-q13. American journal of human genetics 1989,45(2):276-282.
92. Harwood J, Tachibana A, Davis R, Bhattacharyya NP, Meuth M:High rate of multilocus deletion in a human tumor cell line. Human molecular genetics 1993, 2(2):165-171.
93. Baker E, Guo XH, Orsborn AM, Sutherland GR, Callen DF, Hopwood JJ, Morris CP: The morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3. American journal of human genetics 1993,52(1):96-98.
94. Moerland E, Breuning MH, Cornelisse CJ, Cleton-Jansen AM:Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes. British journal of cancer 1997,76(12):1550-1553.
95. Moon RT, Bowerman B, Boutros M, Perrimon N:The promise and perils of Wnt signaling through beta-catenin. Science (New York, NY2002,296(5573):1644-1646.
96. Yost C, Torres M, Miller JR, Huang E, Kimelman D, Moon RT:The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes & development 1996, 10(12):1443-1454.
97. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P:Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996,272(5264):1023-1026.
98. Lee HS, Park MH, Yang SJ, Park KC, Kim NS, Kim YS, Kim DI, Yoo HS, Choi EJ, Yeom YI:Novel candidate targets of Wnt/beta-catenin signaling in hepatoma cells. Life sciences 2007,80(7):690-698.
99. Schmitt-Graeff A, Ertelt-Heitzmann V, Allgaier HP, Olschewski M, Nitschke R, Haxelmans S, Koelble K, Behrens J, Blum HE:Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma. Liver Int 2005,25(4):839-847.
100. Calvisi DF, Conner EA, Ladu S, Lemmer ER, Factor VM, Thorgeirsson SS:Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer. Journal of hepatology 2005,42(6):842-849.
101. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J:Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol 2007, 13(19):2649-2654.
1. Wanless IR, Mawdsley C, Adams R:On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology (Baltimore, Md 1985,5(6):1194-1200.
2. Bioulac-Sage P, Rebouissou S, Sa Cunha A, Jeannot E, Lepreux S, Blanc JF, Blanche H, Le Bail B, Saric J, Laurent-Puig P et al: Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology 2005,128(5):1211-1218.
3. Zhang SH, Cong WM, Wu MC:Focal nodular hyperplasia with concomitant hepatocellular carcinoma:a case report and clonal analysis. Journal of clinical pathology 2004,57(5):556-559.
4. Chen TC, Chou TB, Ng KF, Hsieh LL, Chou YH:Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis. Virchows Arch 2001,438(4):408-411.
5. Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P:Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology (Baltimore, Md 1997,26(4):891-895.
6. Gaffey Mj Fau-Iezzoni JC, Iezzoni Jc Fau-Weiss LM, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. Am JPathol 1996,148(4):1089-1096.
7. Gaffey MJ, Iezzoni JC, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. The American journal of pathology 1996,148(4):1089-1096.
8. Reddy KR, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D, Badalamenti S, Jeffers L, Tzakis A, Schiff ER:Benign and solid tumors of the liver:relationship to sex, age, size of tumors, and outcome. The American surgeon 2001,67(2):173-178.
9. Knowles DM,2nd, Casarella WJ, Johnson PM, Wolff M:The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Medicine 1978,57(3):223-237.
10. Scalori A, Tavani A, Gallus S, La Vecchia C, Colombo M:Oral contraceptives and the risk of focal nodular hyperplasia of the liver:a case-control study. American journal of obstetrics and gynecology 2002,186(2):195-197.
11. Buscarini E, Danesino C, Plauchu H, de Fazio C, Olivieri C, Brambilla G, Menozzi F, Reduzzi L, Blotta P, Gazzaniga P et al: High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia. Ultrasound in medicine & biology 2004,30(9):1089-1097.
12. Ohmoto K, Honda T, Hirokawa M, Mitsui Y, Iguchi Y, Kuboki M, Yamamoto S: Spontaneous regression of focal nodular hyperplasia of the liver. Journal of gastroenterology 2002,37(10):849-853.
13. Cote C:Regression of focal nodular hyperplasia of the liver after oral contraceptive discontinuation. Clinical nuclear medicine 1997,22(9):587-590.
14. Aldinger K, Ben-Menachem Y, Whalen G:Focal nodular hyperplasia of the liver associated with high-dosage estrogens. Archives of internal medicine 1977, 137(3):357-359.
15. Heinemann LA, Weimann A, Gerken G, Thiel C, Schlaud M, DoMinh T:Modern oral contraceptive use and benign liver tumors:the German Benign Liver Tumor Case-Control Study. Eur J Contracept Reprod Health Care 1998,3(4):194-200.
16. Mathieu D, Kobeiter H, Maison P, Rahmouni A, Cherqui D, Zafrani ES, Dhumeaux D: Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology 2000,118(3):560-564.
17. Fukukura Y, Nakashima O, Kusaba A, Kage M, Kojiro M:Angioarchitecture and blood circulation in focal nodular hyperplasia of the liver. Journal of hepatology 1998, 29(3):470-475.
18. Langman G, Hall PD:Focal nodular hyperplasia with calcification and ossification. Pathology 2001,33(3):396-398.
19. De Gaetano AM, Gui B, Macis G, Manfredi R, Di Stasi C:Congenital absence of the portal vein associated with focal nodular hyperplasia in the liver in an adult woman: imaging and review of the literature. Abdominal imaging 2004,29(4):455-459.
20. Wanless IR, Terris B, Bioulac-Sage P:Focal hyperplasia(FH) of liver associated with localized hepatic vein thrombosis:a lesion with some features of'focal nodular hyperplasia'. Mod Pathol 2000,13:191.
21. Mindikoglu AL, Regev A, Levi JU, Casillas J, Schiff ER:Focal nodular hyperplasia in identical twins. The American journal of gastroenterology 2005,100(7):1616-1619.
22. Joyner BL, Jr., Levin TL, Goyal RK, Newman B:Focal nodular hyperplasia of the liver:a sequela of tumor therapy. Pediatric radiology 2005,35(12):1234-1239.
23. Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C:Focal nodular hyperplasia of the liver:a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. The American journal of surgical pathology 1999, 23(12):1441-1454.
24. Nakayama S, Kanbara Y, Nishimura T, Nishida N, Hanioka K, Morita M, Fujita M,
Sakurai K, Hayashi Y:Genome-wide microsatellite analysis of focal nodular hyperplasia:a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma. Journal of hepato-biliary-pancreatic surgery 2006, 13(5):416-420. 25. Baumhueter S, Mendel DB, Conley PB, Kuo CJ, Turk C, Graves MK, Edwards CA, Courtois G, Crabtree GR:HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Genes & development 1990, 4(3):372-379. 26. Cereghini S, Yaniv M, Cortese R:Hepatocyte dedifferentiation and extinction is accompanied by a block in the synthesis of mRNA coding for the transcription factor HNF1/LFB1. Embo J 1990,9(7):2257-2263. 27. Chouard T, Blumenfeld M, Bach I, Vandekerckhove J, Cereghini S, Yaniv M:A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Nucleic acids research 1990,18(19):5853-5863. 28. Shiraishi K, Okita K, Kusano N, Harada T, Kondoh S, Okita S, Ryozawa S, Ohmura R, Noguchi T, Iida Y et al: A comparison of DNA copy number changes detected by
comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas. Oncology 2001,60(2):151-161.
29. Niketeghad F, Decker HJ, Caselmann WH, Lund P, Geissler F, Dienes HP, Schirmacher P:Frequent genomic imbalances suggest commonly altered tumour genes in human hepato carcinogenesis. British journal of cancer 2001,85(5):697-704.
30. Chen YJ, Chen PJ, Lee MC, Yeh SH, Hsu MT, Lin CH:Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. Genes, chromosomes & cancer 2002,35(2):138-143.
31. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
32. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N et al: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science (New York, NY 1997, 277(5322):55-60.
33. Paradis V, Benzekri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, Belghiti J, Vidaud M, Degott C, Bedossa P:Telangiectatic focal nodular hyperplasia:a variant of hepatocellular adenoma. Gastroenterology 2004,126(5):1323-1329.
34. Paradis V, Bieche I, Dargere D, Laurendeau I, Nectoux J, Degott C, Belghiti J, Vidaud M, Bedossa P:A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia. Gastroenterology 2003,124(3):651-659.
35. Schlott T, Ahrens K, Ruschenburg I, Reimer S, Hartmann H, Droese M:Different gene expression of MDM2, GAGE-1,-2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. British journal of cancer 1999,80(1-2):73-78.
36. 王淑芳,苏勤,朱少君,刘节,胡灵芝,李东红：多发性子宫平滑肌瘤的克隆性.中华病理学杂志 2002,31：107-111.
37. Gilliland DG, Blanchard KL, Levy J, Perrin S, Bunn HF:Clonality in myeloproliferative disorders:analysis by means of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 1991,88(15):6848-6852.
38. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW:Methylation of HpaⅡ and HhaⅠ sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. American journal of human genetics 1992,51(6):1229-1239.
39. Melenhorst JJ, Fibbe WE, Smits S, Willemze R, Landegent JE:Aplastic anaemia patients with clonal X-chromosome inactivation pattern in haemopoietic cells exhibit polyclonal TCRgamma and IgH gene rearrangements. British journal of haematology 1996,93(2):326-332.
40. Bannasch P, Schroder CH:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
41. Su Q, Benner A, Hofinann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
42. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31(1):126-133.
43. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
44. 初霞,苏勤,巩丽,张伟,王淑芳,朱少君,李爱宁,冯英明：慢性乙型肝炎和
肝硬化组织中变异肝细胞结节的克隆性.世界华人消化杂志 2005,13(8)：945-952.
45. 巩丽,张宏图,张伟,李爱宁,刘杉,孙耘田,刘贵秋,苏勤：克隆性分析技术在肝脏局灶性结节性增生诊断中的应用.世界华人消化杂志 2006,14(6)：568-575.
46. Bluteau O, Jeannot E, Bioulac-Sage P, Marques JM, Blanc JF, Bui H, Beaudoin JC, Franco D, Balabaud C, Laurent-Puig P et al: Bi-allelic inactivation of TCF1 in hepatic adenomas. Nature genetics 2002,32(2):312-315.
47. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J:Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol 2007, 13(19):2649-2654.
48. Mays ET, Christopherson WM, Barrows GH:Focal nodular hyperplasia of the liver. Possible relationship to oral contraceptives. American journal of clinical pathology 1974,61(6):735-746.
49. Laurent C, Trillaud H, Lepreux S, Balabaud C, Bioulac-Sage P:Association of adenoma and focal nodular hyperplasia:experience of a single French academic center. Comparative hepatology 2003,2(1):6.
50. Edmondson HA, Steiner PE:Primary carcinoma of the liver:a study of 100 cases among 48,900 necropsies. Cancer 1954,7(3):462-503.
51. Friedman LS, Gang DL, Hedberg SE, Isselbacher KJ:Simultaneous occurrence of hepatic adenoma and focal nodular hyperplasia:report of a case and review of the literature. Hepatology (Baltimore, Md 1984,4(3):536-540.
52. Grange JD, Guechot J, Legendre C, Giboudeau J, Darnis F, Poupon R:Liver adenoma and focal nodular hyperplasia in a man with high endogenous sex steroids. Gastroenterology 1987,93(6):1409-1413.
53. Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D:Association of focal nodular hyperplasia and hepatic hemangioma. Gastroenterology 1989,97(1):154-157.
54. Di Carlo I, Urrico GS, Ursino V, Russello D, Puleo S, Latteri F:Simultaneous occurrence of adenoma, focal nodular hyperplasia, and hemangioma of the liver:are they derived from a common origin? Journal of gastroenterology and hepatology 2003,18(2):227-230.
55. Saul SH, Titelbaum DS, Gansler TS, Varello M, Burke DR, Atkinson BF, Rosato EF: The fibrolamellar variant of hepatocellular carcinoma. Its association with focal nodular hyperplasia. Cancer 1987,60(12):3049-3055.
56. Vecchio FM, Fabiano A, Ghirlanda G, Manna R, Massi G:Fibrolamellar carcinoma of the liver:the malignant counterpart of focal nodular hyperplasia with oncocytic change. American journal of clinical pathology 1984,81(4):521-526.
57. Kellner U, Jacobsen A, Kellner A, Mantke R, Roessner A, Rocken C:Comparative genomic hybridization. Synchronous occurrence of focal nodular hyperplasia and hepatocellular carcinoma in the same liver is not based on common chromosomal aberrations. American journal of clinical pathology 2003,119(2):265-271.
58. Cucchetti A, Vivarelli M, De Ruvo N, Bellusci R, Cavallari A:Simultaneous presence of focal nodular hyperplasia and hepatocellular carcinoma:case report and review of the literature. Tumori 2003,89(4):434-436.
59. Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy PF,2nd:Hepatic adenoma and focal nodular hyperplasia:clinical, pathologic, and radiologic features. Gastroenterology 1983,84(5 Pt 1):994-1002.
1. Zender L, Xue W, Cordon-Cardo C, Hannon GJ, Lucito R, Powers S, Flemming P, Spector MS, Lowe SW:Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors. Cold Spring Harbor symposia on quantitative biology 2005,70:251-261.
2. Parkin DM, Bray F, Ferlay J, Pisani P:Global cancer statistics,2002. CA:a cancer journal for clinicians 2005,55(2):74-108.
3. Pisani P, Bray F, Parkin DM:Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. International journal of cancer 2002,97(1):72-81.
4. Montalto G, Cervello M, Giannitrapani L, Dantona F, Terranova A, Castagnetta LA: Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Annals of the New York Academy of Sciences 2002,963:13-20.
5. Macdonald GA:Pathogenesis of hepatocellular carcinoma. Clinics in liver disease 2001,5(1):69-85.
6. Aguayo A, Patt YZ:Liver cancer. Clinics in liver disease 2001,5(2):479-507.
7. Anthony PP, Vogel CL, Barker LF:Liver cell dysplasia:a premalignant condition. Journal of clinical pathology 1973,26(3):217-223.
8. Lee RG, Tsamandas AC, Demetris AJ:Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis:matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology (Baltimore, Md 1997, 26(6):1415-1422.
9. Watanabe S, Okita K, Harada T, Kodama T, Numa Y, Takemoto T, Takahashi T: Morphologic studies of the liver cell dysplasia. Cancer 1983,51(12):2197-2205.
10. Libbrecht L, Craninx M, Nevens F, Desmet V, Roskams T:Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis. Histopathology 2001,39(1):66-73.
11. Gorla GR, Malhi H, Gupta S:Polyploidy associated with oxidative injury attenuates proliferative potential of cells. Journal of cell science 2001,114(Pt 16):2943-2951.
12. 苏勤：人肝细胞癌的癌前期病变.诊断病理学杂志2003,10：112-115.
13. Ganne-Carrie N, Chastang C, Chapel F, Munz C, Pateron D, Sibony M, Deny P, Trinchet JC, Callard P, Guettier C et al: Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis. Hepatology (Baltimore, Md 1996,23(5):1112-1118.
14. Donato MF, Arosio E, Del Ninno E, Ronchi G, Lampertico P, Morabito A, Balestrieri MR, Colombo M:High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity. Hepatology (Baltimore, Md 2001,34(3):523-528.
15. Aihara T, Noguchi S, Sasaki Y, Nakano H, Monden M, Imaoka S:Clonal analysis of precancerous lesion of hepatocellular carcinoma. Gastroenterology 1996, 111(2):455-461.
16. 苏勤,刘彦仿：乙型肝炎、肝硬变中癌前病变的形态学和免疫组织化学观察.第四军医大学学报1995,16(2)：85-88.
17. Okuda K:Hepatocellular carcinoma:recent progress. Hepatology (Baltimore, Md 1992,15(5):948-963.
18. Terminology of nodular hepatocellular lesions. International Working Party. Hepatology (Baltimore, Md 1995,22(3):983-993.
19. Bannasch P SC:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
20. Farber E, Sarma DS:Hepatocarcinogenesis:a dynamic cellular perspective. Laboratory investigation; a journal of technical methods and pathology 1987, 56(1):4-22.
21. Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
22. Su Q, Zerban H, Otto G, Bannasch P:Cytokeratin expression is reduced in glycogenotic clear hepatocytes but increased in ground-glass cells in chronic human and woodchuck hepadnaviral infection. Hepatology (Baltimore, Md 1998, 28(2):347-359.
23. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31(1):126-133.
24. Su Q, Schroder CH, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology (Baltimore, Md 1998,27(4):1109-1120.
25. Su Q, Liu YF, Zhang JF, Zhang SX, Li DF, Yang JJ:Expression of insulin-like growth factor Ⅱ in hepatitis B, cirrhosis and hepatocellular carcinoma:its relationship with hepatitis B virus antigen expression. Hepatology (Baltimore, Md 1994,20(4 Pt 1):788-799.
26. Su Q, Schroder CH, Otto G, Bannasch P:Overexpression of p53 protein is not directly related to hepatitis B x protein expression and is associated with neoplastic progression in hepatocellular carcinomas rather than hepatic preneoplasia. Mutation research 2000,462(2-3):365-380.
27. Henkler F, Waseem N, Golding MH, Alison MR, Koshy R:Mutant p53 but not hepatitis B virus X protein is present in hepatitis B virus-related human hepatocellular carcinoma. Cancer research 1995,55(24):6084-6091.
28. Anthony PP:Hepatocellular carcinoma:an overview. Histopathology 2001, 39(2):109-118.
29. Roncalli M, Bianchi P, Grimaldi GC, Ricci D, Laghi L, Maggioni M, Opocher E, Borzio M, Coggi G:Fractional allelic loss in non-end-stage cirrhosis:correlations with hepatocellular carcinoma development during follow-up. Hepatology (Baltimore, Md 2000,31(4):846-850.
30. Takaishi H, Kitamoto M, Takahashi S, Aikata H, Kawakami Y, Nakanishi T, Nakamura Y, Shimamoto F, Kajiyama G, Ide T:Precancerous hepatic nodules had significant levels of telomerase activity determined by sensitive quantitation using a hybridization protection assay. Cancer 2000,88(2):312-317.
31. Chuma M, Sakamoto M, Yamazaki K, Ohta T, Ohki M, Asaka M, Hirohashi S: Expression profiling in multistage hepatocarcinogenesis:identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology (Baltimore, Md 2003, 37(1):198-207.
32. Tiniakos DG, Brunt EM:Proliferating cell nuclear antigen and Ki-67 labeling in hepatocellular nodules:a comparative study. Liver 1999,19(1):58-68.
33. Libbrecht L, Desmet V, Van Damme B, Roskams T:The immunohistochemical phenotype of dysplastic foci in human liver:correlation with putative progenitor cells. Journal of hepatology 2000,33(1):76-84.
34. Kay A ME, Trepo C, Galibert F.:The HBV HBX gene expressed in E. coli is recognised by sera from hepatitis patients. EMBO J 1985,4(5):1287-1292.
35. Murakami S:Hepatitis B virus X protein:a multifunctional viral regulator. Journal of gastroenterology 2001,36(10):651-660.
36. Xu ZH, Zhao MJ, Li TP:p73beta inhibits transcriptional activities of enhancer I and X promoter in hepatitis B virus more efficiently than p73alpha. World J Gastroenterol 2002,8(6):1094-1097.
37. Su F, Theodosis CN, Schneider RJ:Role of NF-kappaB and myc proteins in apoptosis induced by hepatitis B virus HBx protein. Journal of virology 2001,75(1):215-225.
38. Lin Y, Nomura T, Yamashita T, Dorjsuren D, Tang H, Murakami S:The transactivation and p53-interacting functions of hepatitis B virus X protein are mutually interfering but distinct. Cancer research 1997,57(22):5137-5142.
39. Elmore LW, Hancock AR, Chang SF, Wang XW, Chang S, Callahan CP, Geller DA, Will H, Harris CC:Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proceedings of the National Academy of Sciences of the United States of America 1997,94(26):14707-14712.
40. Chen X, Ko LJ, Jayaraman L, Prives C:p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes & development 1996,10(19):2438-2451.
41. Ahn JY, Jung EY, Kwun HJ, Lee CW, Sung YC, Jang KL:Dual effects of hepatitis B virus X protein on the regulation of cell-cycle control depending on the status of cellular p53. The Journal of general virology 2002,83(Pt 11):2765-2772.
42. Park US, Park SK, Lee YI, Park JG, Lee YI:Hepatitis B virus-X protein upregulates the expression of p21wafl/cipl and prolongs G1-->S transition via a p53-independent pathway in human hepatoma cells. Oncogene 2000,19(30):3384-3394.
43. Shimazu T, Takada S, Ueno Y, Hayashi Y, Koike K:Post-transcriptional control of the level of mRNA by hepatitis B virus X gene in the transient expression system using human hepatic cells. Genes Cells 1998,3(7):477-484.
44. Ogden SK, Lee KC, Barton MC:Hepatitis B viral transactivator HBx alleviates p53-mediated repression of alpha-fetoprotein gene expression. The Journal of biological chemistry 2000,275(36):27806-27814.
45. Arbuthnot P, Capovilla A, Kew M:Putative role of hepatitis B virus X protein in hepatocarcinogenesis:effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. Journal of gastroenterology and hepatology 2000, 15(4):357-368.
46. 王兆文,彭志海,李克,裘国强,张益,顾炜：p16影响乙肝病毒相关性肝细胞肝癌的发生.中华病理学杂志2003,25：356-358.
47. Fukushima K, Ueno Y, Yamagiwa Y, Yamakawa M, Iwasaki T, Ishii M, Toyota T, Shimosegawa T:Correlation between p21(wafl) and p16(INK4a) expression in hepatocellular carcinoma. Hepatol Res 2001,20(1):52-67.
48. Becker SA, Lee TH, Butel JS, Slagle BL:Hepatitis B virus X protein interferes with cellular DNA repair. Journal of virology 1998,72(1):266-272.
49. Jia L, Wang XW, Harris CC:Hepatitis B virus X protein inhibits nucleotide excision repair. International journal of cancer 1999,80(6):875-879.
50. Capovilla A, Carmona S, Arbuthnot P:Hepatitis B virus X-protein binds damaged DNA and sensitizes liver cells to ultraviolet irradiation. Biochemical and biophysical research communications 1997,232(1):255-260.
51. Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A:Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proceedings of the National Academy of Sciences of the United States of America 1990,87(17):6599-6603.
52. Noda K, Yoshihara H, Suzuki K, Yamada Y, Kasahara A, Hayashi N, Fusamoto H, Kamada T:Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma--its relationship to alcohol drinking and the age of transfusion. Alcoholism, clinical and experimental research 1996,20(1 Suppl):95A-100A.
53. Bahnassi AA, Zekri AR, El-Houssini S, Mokhtar NM, Abdel-Aziz AO, Sherif GM, El-Mishad AM, Khaled HM:Hepatitis C virus-NS3P in relation to p53, p21waf, mdm2, p21-ras and c-erbB2 in hepatocarcinogenesis. Journal of gastroenterology and hepatology 2005,20(11):1731-1740.
54. Baek KH, Park HY, Kang CM, Kim SJ, Jeong SJ, Hong EK, Park JW, Sung YC, Suzuki T, Kim CM et al: Overexpression of hepatitis C virus NS5A protein induces chromosome instability via mitotic cell cycle dysregulation. Journal of molecular biology 2006,359(1):22-34.
55. Tung P RR, Fan ST, Wong J.:Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.. Ann Surg 2000, 232:100.
56. NIH:National institutes of hearth consensus development conference panel statement:management of hepatitis C. Hepatology (Baltimore, Md 1997,26:2.
57. Lee YI, Lee S, Das GC, Park US, Park SM, Lee YI:Activation of the insulin-like growth factor Ⅱ transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma. Oncogene 2000,19(33):3717-3726.
58. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC:Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 1991,350(6317):377-378.
59. Hayashi H, Sugio K, Matsumata T, Adachi E, Urata K, Tanaka S, Sugimachi K:The mutation of codon 249 in the p53 gene is not specific in Japanese hepatocellular carcinoma. Liver 1993,13(5):279-281.
60. Bailey MA, Brunt EM:Hepatocellular carcinoma:predisposing conditions and precursor lesions. Gastroenterology clinics of North America 2002,31(2):641-662.
61. Perlmutter DH:Liver injury in alpha 1-antitrypsin deficiency. Clinics in liver disease 2000,4(2):387-408, ⅵ.
62. Sternlieb I:Wilson's disease. Clinics in liver disease 2000,4(1):229-239, ⅷ-ⅸ.
63. Issa JP:Aging, DNA methylation and cancer. Critical reviews in oncology/hematology 1999,32(1):31-43.
64. Huang J, Zhang X, Zhang M, Zhu JD, Zhang YL, Lin Y, Wang KS, Qi XF, Zhang Q, Liu GZ et al: Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma. Carcinogenesis 2007,28(5):1094-1103.
65. Shih YL, Shyu RY, Hsieh CB, Lai HC, Liu KY, Chu TY, Lin YW:Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer 2006,107(3):579-590.
66. Kondo Y, Kanai Y, Sakamoto M, Mizokami M, Ueda R, Hirohashi S:Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology (Baltimore, Md 2000, 32(5):970-979.
67. Su H, Zhao J, Xiong Y, Xu T, Zhou F, Yuan Y, Zhang Y, Zhuang SM:Large-scale analysis of the genetic and epigenetic alterations in hepatocellular carcinoma from Southeast China. Mutation research 2008,641(1-2):27-35.
68. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
69. Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P:Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. British journal of cancer 2005,
92(5):935-941.
70. Yeh SH, Chen PJ, Shau WY, Chen YW, Lee PH, Chen JT, Chen DS:Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma. Gastroenterology 2001,121(3):699-709.
71. Mori T, Nomoto S, Koshikawa K, Fujii T, Sakai M, Nishikawa Y, Inoue S, Takeda S, Kaneko T, Nakao A:Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepato cellular carcinoma. Liver Int 2005, 25(2):380-388.
72. Sun M, Eshleman JR, Ferrell LD, Jacobs Q Sudilovsky EC, Tuthill R, Hussein MR, Sudilovsky O:An early lesion in hepatic carcinogenesis:loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region. Hepatology (Baltimore, Md 2001,33(6):1415-1424.
73. Riva P, Crosti F, Orzan F, Dalpra L, Mortini P, Parafioriti A, Pollo B, Fuhrman Conti A, Miozzo M, Larizza L:Mapping of candidate region for chordoma development to 1p36.13 by LOH analysis. International journal of cancer 2003,107(3):493-497.
74. De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC, Jirtle RL:Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor Ⅱ receptor locus in human hepatocellular tumors. Oncogene 1995,10(9):1725-1729.
75. Ozaki I, Mizuta T, Zhao G, Yotsumoto H, Hara T, Kajihara S, Hisatomi A, Sakai T, Yamamoto K:Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma. Cancer research 2000,60(22):6519-6525.
76. Park WS, Lee JH, Park JY, Jeong SW, Shin MS, Kim HS, Lee SK, Lee SN, Lee SH, Park CG et al:Genetic analysis of the liver putative tumor suppressor (LPTS) gene in hepatocellular carcinomas. Cancer letters 2002,178(2):199-207.
77. Wu X, Jia HL, Wang YF, Ren N, Ye QH, Sun HC, Wang L, Liu YK, Tang ZY, Qin LX: HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma. Oncogene 2006,25(12):1832-1840.
78. Nagai H, Emi M, Terada Y, Baba M, Shimizu M, Konishi N, Kaneko S, Kobayashi K, Yumoto Y, Ghazizadeh M et al:DNA alterations during multi-step development of human hepatocellular carcinomas revealed by laser capture microdissection. Hepatol Res 2003,26(3):199-208.
79. Anders RA, Yerian LM, Tretiakova M, Davison JM, Quigg RJ, Domer PH, Hoberg J, Hart J:cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis. The American journal of pathology 2003, 162(3):991-1000.
80. Nam SW, Park JY, Ramasamy A, Shevade S, Islam A, Long PM, Park CK, Park SE, Kim SY, Lee SH et al: Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling. Hepatology (Baltimore, Md 2005, 42(4):809-818.
81. Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN, Khitrov G, Zhang W, Villanueva A et al: A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology 2006,131 (6):1758-1767.
82. Hayashi D:[Study on the expression of oncogene mRNA in hepatocellular carcinoma using in situ hybridization technique]. Nippon Geka Gakkai zasshi 1994, 95(11):814-822.
83. 林月珍,丁濂,陈晋彦：癌前变异肝细胞c-myc、N-ras mRNA的表达及其与分化的关系.中华肿瘤杂志1993,15(2)：97.
84. Niu ZS, Li BK, Wang M:Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues. World J Gastroenterol 2002,8(5):822-826.
85. Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH, Koshy R:The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature 1990,343(6257):457-461.
86. 郑杰,武忠弼,阮幼冰,等：二乙基亚硝胺诱发大鼠肝癌前病变中c-myc、N-ras和γ-GT酶表达的相关性研究.肿瘤1995,15(6)：462.
87. Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS:Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. The American journal of pathology 1996, 149(2):407-428.
88. De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL:M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nature genetics 1995, 11(4):447-449.
89. Seo JH, Park BC:Expression of insulin-like growth factor II in chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. Gan to kagaku ryoho 1995,22 Suppl 3:292-307.
90. Cariani E, Dubois N, Lasserre C, Briand P, Brechot C:Insulin-like growth factor Ⅱ (IGF-II) mRNA expression during hepatocarcinogenesis in transgenic mice. Journal of hepatology 1991,13(2):220-226.
91. Lamas E, Le Bail B, Housset C, Boucher O, Brechot C:Localization of insulin-like growth factor-Ⅱ and hepatitis B virus mRNAs and proteins in human hepatocellular carcinomas. Laboratory investigation; a journal of technical methods and pathology 1991,64(1):98-104.
92. Yang D, Faris R, Hixson D, Affigne S, Rogler CE:Insulin-like growth factor II blocks apoptosis of N-myc2-expressing woodchuck liver epithelial cells. Journal of virology 1996,70(9):6260-6268.
93. 杨冬华,徐重,杨波,等：不同肝病患者肝细胞中胰岛素样生长因子及其受体的表达.中华医学杂志 1996,26(1)：50.
94. Hsia CC, Kleiner DE, Jr., Axiotis CA, Di Bisceglie A, Nomura AM, Stemmermann GN, Tabor E:Mutations of p53 gene in hepatocellular carcinoma:roles of hepatitis B virus and aflatoxin contamination in the diet. Journal of the National Cancer Institute 1992,84(21):1638-1641.
95. Teramoto T, Satonaka K, Kitazawa S, Fujimori T, Hayashi K, Maeda S:p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. Cancer research 1994,54(1):231-235.
96. Ojanguren I, Ariza A, Castella EM, Fernandez-Vasalo A, Mate JL, Navas-Palacios JJ: p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia, cirrhosis and hepatocellular carcinoma. Histopathology 1995,26(1):63-68.
97. Livni N, Eid A, Ilan Y, Rivkind A, Rosenmann E, Blendis LM, Shouval D, Galun E: p53 expression in patients with cirrhosis with and without hepatocellular carcinoma. Cancer 1995,75(10):2420-2426.
98. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC:Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer research 1998, 58(10):2196-2199.
99. Durkin ME, Yuan BZ, Thorgeirsson SS, Popescu NC:Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7). Gene 2002, 288(1-2):119-127.
100. Park SW, Durkin ME, Thorgeirsson SS, Popescu NC:DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma. International
journal of oncology 2003,23(1):133-137.
101. Plaumann M, Seitz S, Frege R, Estevez-Schwarz L, Scherneck S:Analysis of DLC-1 expression in human breast cancer. Journal of cancer research and clinical oncology 2003,129(6):349-354.
102. Ng 10, Liang ZD, Cao L, Lee TK:DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer research 2000,60(23):6581-6584.
103. Wong CM, Lee JM, Ching YP, Jin DY, Ng IO:Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer research 2003,63(22):7646-7651.
104. Zhou X, Thorgeirsson SS, Popescu NC:Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. Oncogene 2004,23(6):1308-1313.
105. Piao Z, Park YN, Kim H, Park C:Clonality of large regenerative nodules in liver cirrhosis. Liver 1997,17(5):251-256.
106. Theise ND:Cirrhosis and hepatocellular neoplasia:more like cousins than like parent and child. Gastroenterology 1996, 111(2):526-528.
107. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
108. Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S et al: Genotype-phenotype correlation in hepatocellular adenoma:new classification and relationship with HCC. Hepatology 2006,43(3):515-524.
109. Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E et al: A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996,380(6570):152-154.
110. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001,409(6822):860-921.
111. 张建军,安倩：微卫星与肿瘤.癌症2000,19(10)：948-950.
112. Bailey AD, Pavelitz T, Weiner AM:The microsatellite sequence (CT)n x (GA)n promotes stable chromosomal integration of large tandem arrays of functional human U2 small nuclear RNA genes. Molecular and cellular biology 1998,18(4):2262-2271.
113. 周晓东：微卫星不稳定性与肿瘤.国外医学肿瘤学分册1996,23：212-215.
114. Meloni R, Albanese V, Ravassard P, Treilhou F, Mallet J:A tetranucleotide polymorphic microsatellite, located in the first intron of the tyrosine hydroxylase gene, acts as a transcription regulatory element in vitro. Human molecular genetics 1998, 7(3):423-428.
115. Kashi Y, King D, Soller M:Simple sequence repeats as a source of quantitative genetic variation. Trends Genet 1997,13(2):74-78.
116. Gerber HP, Seipel K, Georgiev O, Hofferer M, Hug M, Rusconi S, Schaffner W: Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science (New York, NY 1994,263(5148):808-811.
117. Stallings RL:Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence:implications for human genetic diseases. Genomics 1994,21(1):116-121.
118. Sia EA, Jinks-Robertson S, Petes TD:Genetic control of microsatellite stability. Mutation research 1997,383(1):61-70.
119. Subramanian S, Mishra RK, Singh L:Genome-wide analysis of microsatellite repeats in humans:their abundance and density in specific genomic regions. Genome biology 2003,4(2):R13.
120. Jurka J, Pethiyagoda C:Simple repetitive DNA sequences from primates:compilation and analysis. Journal of molecular evolution 1995,40(2):120-126.
121. Beckman JS, Weber JL:Survey of human and rat microsatellites. Genomics 1992, 12(4):627-631.
122. Sheu JC, Lin YW, Chou HC, Huang GT, Lee HS, Lin YH, Huang SY, Chen CH, Wang JT, Lee PH et al:Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan. British journal of cancer 1999,80(3-4):468-476.
123. Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S et al:Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype. Cancer research 1997,57(10):1986-1990.
124. Piao Z, Park C, Park JH, Kim H:Allelotype analysis of hepatocellular carcinoma. International journal of cancer 1998,75(1):29-33.
125. 方嬿,李国辉,卓子兰：20例原发性肝癌实体瘤的细胞遗传学研究.中国优生与遗传杂志1996,4：34-37.
126. 王辉云,关新元,方嬿：肝癌染色体DNA拷贝数的变化及其与临床病理和预后的关系.癌症1999,18：509-513.
127. 李升平,王辉云,张昌卿,冯启胜,余杏娟,陈敏山,黄丽惜,黄平,郭荣平,林小军,张亚奇,李锦清,李国辉,曾益新：原发性肝癌全基因组杂合性缺失的研究.中华医学杂志 2000,80(8)：577-581.
128. Becker SA, Zhou YZ, Slagle BL:Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer research 1996, 56(21):5092-5097.
129. Piao Z, Kim H, Jeon BK, Lee WJ, Park C:Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma. Cancer 1997,80(5):865-872.
2. Reddy KR, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D, Badalamenti S, Jeffers L, Tzakis A, Schiff ER:Benign and solid tumors of the liver:relationship to sex, age, size of tumors, and outcome. The American surgeon 2001,67(2):173-178.
3. Knowles DM,2nd, Casarella WJ, Johnson PM, Wolff M:The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Medicine 1978,57(3):223-237.
4. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
5. Bannasch P, Schroder CH:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
6. Chen YW, Jeng YM, Yeh SH, Chen PJ:P53 gene and Wnt signaling in benign neoplasms:beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia. Hepatology 2002,36(4 Pt 1):927-935.
7. Ishak KG AP, Sobin LH:Definition and explanatory notes:liver. In:Ishak KG, Anthony PR, Sobin LH, eds. Histological typing of tumors of the liver. International Histological Classification of Tumors Berlin:WHO,1994:9-36.
8. Wanless IR, Mawdsley C, Adams R:On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology (Baltimore, Md 1985,5(6):1194-1200.
9. Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C:Focal nodular hyperplasia of the liver:a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. The American journal of surgical pathology 1999, 23(12):1441-1454.
10. Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P:Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology (Baltimore, Md 1997,26(4):891-895.
11. Gaffey Mj Fau-Iezzoni JC, Iezzoni Jc Fau-Weiss LM, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 1996,148(4):1089-1096.
12. Paradis V, Benzekri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, Belghiti J, Vidaud M, Degott C, Bedossa P:Telangiectatic focal nodular hyperplasia:a variant of hepatocellular adenoma. Gastroenterology 2004,126(5):1323-1329.
13. Nakayama S, Kanbara Y, Nishimura T, Nishida N, Hanioka K, Morita M, Fujita M, Sakurai K, Hayashi Y:Genome-wide microsatellite analysis of focal nodular hyperplasia:a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma. Journal of hepato-biliary-pancreatic surgery 2006, 13(5):416-420.
14. Chen YJ, Chen PJ, Lee MC, Yeh SH, Hsu MT, Lin CH:Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. Genes, chromosomes & cancer 2002,35(2):138-143.
15. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
16. Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
17. 巩丽,张宏图,张伟,李爱宁,刘杉,孙耘田,刘贵秋,苏勤：克隆性分析技术在肝脏局灶性结节性增生诊断中的应用.世界华人消化杂志 2006,14(6)：568-575.
18. Zhang SH, Cong WM, Wu MC:Focal nodular hyperplasia with concomitant hepatocellular carcinoma:a case report and clonal analysis. Journal of clinical pathology 2004,57(5):556-559.
19. Chen TC, Chou TB, Ng KF, Hsieh LL, Chou YH:Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis. Virchows Arch 2001,438(4):408-411.
20. Kellner U, Jacobsen A, Kellner A, Mantke R, Roessner A, Rocken C:Comparative genomic hybridization. Synchronous occurrence of focal nodular hyperplasia and hepatocellular carcinoma in the same liver is not based on common chromosomal aberrations. American journal of clinical pathology 2003,119(2):265-271.
21. 苏勤：人肝细胞癌的癌前期病变.诊断病理学杂志2003,10：112-115.
22. 初霞,苏勤,巩丽,张伟,王淑芳,朱少君,李爱宁,冯英明：慢性乙型肝炎和
肝硬化组织中变异肝细胞结节的克隆性.世界华人消化杂志 2005,13(8)：945-952.
23. Edmondson HA, Steiner PE:Primary carcinoma of the liver:a study of 100 cases among 48,900 necropsies. Cancer 1954,7(3):462-503.
24. 苏勤,刘彦仿：乙型肝炎、肝硬变中癌前病变的形态学和免疫组织化学观察.第四军医大学学报1995,16(2)：85-88.
25. Nesbitt MN:Chimeras vs X inactivation mosaics:significance of differences in pigment distribution. Developmental biology 1974,38(1):202-207.
26. Ochiai T, Ueda K, Urata Y, Yamano T, Konishi E, Ogino A, Kawai K, Itoi H, Sonoyama T, Yamagishi H et al: [Clonal analysis of hepatocellular carcinoma]. Gan to kagaku ryoho 1996,23 Suppl 2:182-188.
27. Nagai H, Pineau P, Tiollais P, Buendia MA, Dejean A:Comprehensive allelotyping of human hepatocellular carcinoma. Oncogene 1997,14(24):2927-2933.
28. Sun M, Eshleman JR, Ferrell LD, Jacobs G, Sudilovsky EC, Tuthill R, Hussein MR, Sudilovsky O:An early lesion in hepatic carcinogenesis:loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region. Hepatology (Baltimore, Md 2001,33(6):1415-1424.
29. Maggioni M, Coggi G, Cassani B, Bianchi P, Romagnoli S, Mandelli A, Borzio M, Colombo P, Roncalli M:Molecular changes in hepatocellular dysplastic nodules on microdissected liver biopsies. Hepatology 2000,32(5):942-946.
30. Kondo Y, Kanai Y, Sakamoto M, Mizokami M, Ueda R, Hirohashi S:Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology 2000,32(5):970-979.
31. Zhang SH, Cong WM, Xian ZH, Wu MC:Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China. World J Gastroenterol 2005,11(20):3034-3039.
32. Kahng YS, Lee YS, Kim BK, Park WS, Lee JY, Kang CS:Loss of heterozygosity of chromosome 8p and 11p in the dysplastic nodule and hepatocellular carcinoma. Journal of gastroenterology and hepatology 2003,18(4):430-436.
33. Kim H, Lee MJ, Kim MR, Chung IP, Kim YM, Lee JY, Jang JJ:Expression of cyclin D1, cyclin E, cdk4 and loss of heterozygosity of 8p,13q,17p in hepatocellular carcinoma:comparison study of childhood and adult hepatocellular carcinoma. Liver 2000,20(2):173-178.
34. Chan KL, Lee JM, Guan XY, Fan ST, Ng IO:High-density allelotyping of chromosome 8p in hepato cellular carcinoma and clinicopathologic correlation. Cancer 2002,94(12):3179-3185.
35. Sheu JC, Lin YW, Chou HC, Huang GT, Lee HS, Lin YH, Huang SY, Chen CH, Wang JT, Lee PH et al:Loss of heterozygosity and microsatellite instability in hepato cellular carcinoma in Taiwan. British journal of cancer 1999,80(3-4):468-476.
36. Wong CM, Lee JM, Ching YP, Jin DY, Ng IO:Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer research 2003,63(22):7646-7651.
37. Dore MP, Realdi G, Mura D, Onida A, Massarelli G, Dettori G, Graham DY, Sepulveda AR:Genomic instability in chronic viral hepatitis and hepatocellular carcinoma. Human pathology 2001,32(7):698-703.
38. Henegariu O, Heerema NA, Dlouhy SR, Vance GH, Vogt PH:Multiplex PCR:critical parameters and step-by-step protocol. BioTechniques 1997,23(3):504-511.
39. Piao Z, Park C, Park JH, Kim H:Allelotype analysis of hepatocellular carcinoma. International journal of cancer 1998,75(1):29-33.
40. Wong CM, Lee JM, Lau TC, Fan ST, Ng IO:Clinicopathological significance of loss of heterozygosity on chromosome 13q in hepatocellular carcinoma. Clin Cancer Res 2002,8(7):2266-2272.
41. Maruyama K, Ochiai A, Akimoto S, Nakamura S, Baba S, Moriya Y, Hirohashi S: Cytoplasmic beta-catenin accumulation as a predictor of hematogenous metastasis in human co lorectal cancer. Oncology 2000,59(4):302-309.
42. Bosch FX, Ribes J, Borras J:Epidemiology of primary liver cancer. Seminars in liver disease 1999,19(3):271-285.
43. Edmondson HA:Tumors of the liver and intrahepatic bile ducts. In:Atlas of tumor pathology. Washington (DC):Armed Forces Institute of Pathology; 1958.
44. Scalori A, Tavani A, Gallus S, La Vecchia C, Colombo M:Oral contraceptives and the risk of focal nodular hyperplasia of the liver:a case-control study. American journal of obstetrics and gynecology 2002,186(2):195-197.
45. Mathieu D, Kobeiter H, Cherqui D, Rahmouni A, Dhumeaux D:Oral contraceptive intake in women with focal nodular hyperplasia of the liver. Lancet 1998, 352(9141):1679-1680.
46. Makhlouf HR, Abdul-Al HM, Goodman ZD:Diagnosis of focal nodular hyperplasia of the liver by needle biopsy. Human pathology 2005,36(11):1210-1216.
47. Bioulac-Sage P, Balabaud C, Bedossa P, Scoazec JY, Chiche L, Dhillon AP, Ferrell L, Paradis V, Roskams T, Vilgrain V et al:Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia:Bordeaux update. Journal of hepatology 2007, 46(3):521-527.
48. Gaiani S, Piscaglia F, Serra C, Bolondi L:Hemodynamics in focal nodular hyperplasia. Journal of hepatology 1999,31(3):576.
49. Fukukura Y, Nakashima O, Kusaba A, Kage M, Kojiro M:Angioarchitecture and blood circulation in focal nodular hyperplasia of the liver. Journal of hepatology 1998, 29(3):470-475.
50. Vecchio FM, Fabiano A, Ghirlanda G, Manna R, Massi G:Fibrolamellar carcinoma of the liver:the malignant counterpart of focal nodular hyperplasia with oncocytic change. American journal of clinical pathology 1984,81(4):521-526.
51. Gaffey MJ, Iezzoni JC, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. The American journal of pathology 1996,148(4):1089-1096.
52. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31 (1):126-133.
53. Farber E, Sarma DS:Hepatocarcinogenesis:a dynamic cellular perspective. Laboratory investigation; a journal of technical methods and pathology 1987, 56(1):4-22.
54. Field D, Wills C:Long, polymorphic microsatellites in simple organisms. Proceedings 1996,263(1367):209-215.
55. Hancock JM:The contribution of slippage-like processes to genome evolution. Journal of molecular evolution 1995,41(6):1038-1047.
56. 张建军,安倩：微卫星与肿瘤.癌症2000,19(10)：948-950.
57. Stallings RL:Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence:implications for human genetic diseases. Genomics 1994,21(1):116-121.
58. Lyon MF:X-chromosome inactivation and developmental patterns in mammals. Biological reviews of the Cambridge Philosophical Society 1972,47(1):1-35.
59. Gilliland DG, Blanchard KL, Levy J, Perrin S, Bunn HF:Clonality in myeloproliferative disorders:analysis by means of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 1991,88(15):6848-6852.
60. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW:Methylation of HpaⅡ and HhaⅠ sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. American journal of human genetics 1992,51 (6):1229-1239.
61. Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S et al: Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype. Cancer research 1997,57(10):1986-1990.
62. 方嬿,李国辉,卓子兰：20例原发性肝癌实体瘤的细胞遗传学研究.中国优生与遗传杂志1996,4：34-37.
63. 王辉云,关新元,方嬿：肝癌染色体DNA拷贝数的变化及其与临床病理和预后的关系.癌症1999,18：509-513.
64. Schleiermacher G, Delattre O, Peter M, Mosseri V, Delonlay P, Vielh P, Thomas G, Zucker JM, Magdelenat H, Michon J:Clinical relevance of loss heterozygosity of the short arm of chromosome 1 in neuroblastoma:a single-institution study. International journal of cancer 1996,69(2):73-78.
65. Bieche I, Champeme MH, Matifas F, Cropp CS, Callahan R, Lidereau R:Two distinct regions involved in lp deletion in human primary breast cancer. Cancer research 1993, 53(9):1990-1994.
66. Yeh SH, Chen PJ, Chen HL, Lai MY, Wang CC, Chen DS:Frequent genetic alterations at the distal region of chromosome lp in human hepatocellular carcinomas. Cancer research 1994,54(15):4188-4192.
67. Kraus JA, Albrecht S, Wiestler OD, von Schweinitz D, Pietsch T:Loss of heterozygosity on chromosome 1 in human hepatoblastoma. International journal of cancer 1996,67(4):467-471.
68. Becker SA, Zhou YZ, Slagle BL:Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer research 1996, 56(21):5092-5097.
69. Steinemann D, Skawran B, Becker T, Tauscher M, Weigmann A, Wingen L, Tauscher S, Hinrichsen T, Hertz S, Flemming P et al: Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization. Clin Gastroenterol Hepatol 2006,4(10):1283-1291.
70. Piao Z, Kim NG, Kim H, Park C:Deletion mapping on the short arm of chromosome 8 in hepatocellular carcinoma. Cancer letters 1999,138(1-2):227-232.
71. Liao C, Zhao M, Song H, Uchida K, Yokoyama KK, Li T:Identification of the gene for a novel liver-related putative tumor suppressor at a high-frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma. Hepatology 2000,32(4 Pt 1):721-727.
72. Fujiwara Y, Ohata H, Kuroki T, Koyama K, Tsuchiya E, Monden M, Nakamura Y: Isolation of a candidate tumor suppressor gene on chromosome 8p21.3-p22 that is homologous to an extracellular domain of the PDGF receptor beta gene. Oncogene 1995,10(5):891-895.
73. Aaronson SA:Growth factors and cancer. Science 1991,254(5035):1146-1153.
74. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC:Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer research 1998, 58(10):2196-2199.
75. Durkin ME, Yuan BZ, Thorgeirsson SS, Popescu NC:Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7). Gene 2002, 288(1-2):119-127.
76. Rogler CE, Sherman M, Su CY, Shafritz DA, Summers J, Shows TB, Henderson A, Kew M:Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science (New York,NY1985,230(4723):319-322.
77. Liu H, Ling Y, Gong Y, Sun Y, Hou L, Zhang B:DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation. Molecular and cellular biochemistry 2007,300(1-2):249-258.
78. Kuroki T, Fujiwara Y, Nakamori S, Imaoka S, Kanematsu T, Nakamura Y:Evidence for the presence of two tumour-suppressor genes for hepatocellular carcinoma on chromosome 13q. British journal of cancer 1995,72(2):383-385.
79. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986,323(6089):643-646.
80. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G:Identification of the breast cancer susceptibility gene BRCA2. Nature 1995,378(6559):789-792.
81. Tsukamoto K, Ito N, Yoshimoto M, Iwase T, Tada T, Kasumi F, Nakamura Y, Emi M: Two distinct commonly deleted regions on chromosome 13q suggest involvement of BRCA2 and retinoblastoma genes in sporadic breast carcinomas. Cancer 1996, 78(9):1929-1934.
82. Grimmond SM, Palmer JM, Walters MK, Scott C, Nancarrow DJ, Teh BT, Elmes C, Pyke C, Khoo SK, Bennett I et al: Confirmation of susceptibility locus on chromosome 13 in Australian breast cancer families. Human genetics 1996, 98(1):80-85.
83. 邵建永,李晓明,刘宗石,林汉良：原发性肝癌患者17号和16号染色体等位基因杂合性丢失的研究.中华医学杂志1999,79(6)：428-430.
84. Tsuda H, Zhang WD, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S:Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America 1990,87(17):6791-6794.
85. Yeh SH, Chen PJ, Lai MY, Chen DS:Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma:association with elevated alpha-fetoprotein production. Gastroenterology 1996,110(1):184-192.
86. Fujimoto Y, Hampton LL, Wirth PJ, Wang NJ, Xie JP, Thorgeirsson SS:Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. Cancer research 1994,54(1):281-285.
87. Marchio A, Meddeb M, Pineau P, Danglot G, Tiollais P, Bernheim A, Dejean A: Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization. Genes, chromosomes & cancer 1997, 18(1):59-65.
88. Zhao X, Li J, He Y, Lan F, Fu L, Guo J, Zhao R, Ye Y, He M, Chong W et al: A novel growth suppressor gene on chromosome 17p13.3 with a high frequency of mutation in human hepatocellular carcinoma. Cancer research 2001,61(20):7383-7387.
89. Kochetkova M, McKenzie OL, Bais AJ, Martin JM, Secker GA, Seshadri R, Powell JA, Hinze SJ, Gardner AE, Spendlove HE et al: CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3. Cancer research 2002,62(16):4599-4604.
90. Kumar R, Neilsen PM, Crawford J, McKirdy R, Lee J, Powell JA, Saif Z, Martin JM, Lombaerts M, Cornelisse CJ et al: FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex. Cancer research 2005,65(24):11304-11313.
91. Francke U, Darras BT, Zander NF, Kilimann MW:Assignment of human genes for
phosphorylase kinase subunits alpha (PHKA) to Xq12-q13 and beta (PHKB) to 16q12-q13. American journal of human genetics 1989,45(2):276-282.
92. Harwood J, Tachibana A, Davis R, Bhattacharyya NP, Meuth M:High rate of multilocus deletion in a human tumor cell line. Human molecular genetics 1993, 2(2):165-171.
93. Baker E, Guo XH, Orsborn AM, Sutherland GR, Callen DF, Hopwood JJ, Morris CP: The morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3. American journal of human genetics 1993,52(1):96-98.
94. Moerland E, Breuning MH, Cornelisse CJ, Cleton-Jansen AM:Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes. British journal of cancer 1997,76(12):1550-1553.
95. Moon RT, Bowerman B, Boutros M, Perrimon N:The promise and perils of Wnt signaling through beta-catenin. Science (New York, NY2002,296(5573):1644-1646.
96. Yost C, Torres M, Miller JR, Huang E, Kimelman D, Moon RT:The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes & development 1996, 10(12):1443-1454.
97. Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P:Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 1996,272(5264):1023-1026.
98. Lee HS, Park MH, Yang SJ, Park KC, Kim NS, Kim YS, Kim DI, Yoo HS, Choi EJ, Yeom YI:Novel candidate targets of Wnt/beta-catenin signaling in hepatoma cells. Life sciences 2007,80(7):690-698.
99. Schmitt-Graeff A, Ertelt-Heitzmann V, Allgaier HP, Olschewski M, Nitschke R, Haxelmans S, Koelble K, Behrens J, Blum HE:Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma. Liver Int 2005,25(4):839-847.
100. Calvisi DF, Conner EA, Ladu S, Lemmer ER, Factor VM, Thorgeirsson SS:Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer. Journal of hepatology 2005,42(6):842-849.
101. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J:Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol 2007, 13(19):2649-2654.
1. Wanless IR, Mawdsley C, Adams R:On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology (Baltimore, Md 1985,5(6):1194-1200.
2. Bioulac-Sage P, Rebouissou S, Sa Cunha A, Jeannot E, Lepreux S, Blanc JF, Blanche H, Le Bail B, Saric J, Laurent-Puig P et al: Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology 2005,128(5):1211-1218.
3. Zhang SH, Cong WM, Wu MC:Focal nodular hyperplasia with concomitant hepatocellular carcinoma:a case report and clonal analysis. Journal of clinical pathology 2004,57(5):556-559.
4. Chen TC, Chou TB, Ng KF, Hsieh LL, Chou YH:Hepatocellular carcinoma associated with focal nodular hyperplasia. Report of a case with clonal analysis. Virchows Arch 2001,438(4):408-411.
5. Paradis V, Laurent A, Flejou JF, Vidaud M, Bedossa P:Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology (Baltimore, Md 1997,26(4):891-895.
6. Gaffey Mj Fau-Iezzoni JC, Iezzoni Jc Fau-Weiss LM, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. Am JPathol 1996,148(4):1089-1096.
7. Gaffey MJ, Iezzoni JC, Weiss LM:Clonal analysis of focal nodular hyperplasia of the liver. The American journal of pathology 1996,148(4):1089-1096.
8. Reddy KR, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D, Badalamenti S, Jeffers L, Tzakis A, Schiff ER:Benign and solid tumors of the liver:relationship to sex, age, size of tumors, and outcome. The American surgeon 2001,67(2):173-178.
9. Knowles DM,2nd, Casarella WJ, Johnson PM, Wolff M:The clinical, radiologic, and pathologic characterization of benign hepatic neoplasms. Alleged association with oral contraceptives. Medicine 1978,57(3):223-237.
10. Scalori A, Tavani A, Gallus S, La Vecchia C, Colombo M:Oral contraceptives and the risk of focal nodular hyperplasia of the liver:a case-control study. American journal of obstetrics and gynecology 2002,186(2):195-197.
11. Buscarini E, Danesino C, Plauchu H, de Fazio C, Olivieri C, Brambilla G, Menozzi F, Reduzzi L, Blotta P, Gazzaniga P et al: High prevalence of hepatic focal nodular hyperplasia in subjects with hereditary hemorrhagic telangiectasia. Ultrasound in medicine & biology 2004,30(9):1089-1097.
12. Ohmoto K, Honda T, Hirokawa M, Mitsui Y, Iguchi Y, Kuboki M, Yamamoto S: Spontaneous regression of focal nodular hyperplasia of the liver. Journal of gastroenterology 2002,37(10):849-853.
13. Cote C:Regression of focal nodular hyperplasia of the liver after oral contraceptive discontinuation. Clinical nuclear medicine 1997,22(9):587-590.
14. Aldinger K, Ben-Menachem Y, Whalen G:Focal nodular hyperplasia of the liver associated with high-dosage estrogens. Archives of internal medicine 1977, 137(3):357-359.
15. Heinemann LA, Weimann A, Gerken G, Thiel C, Schlaud M, DoMinh T:Modern oral contraceptive use and benign liver tumors:the German Benign Liver Tumor Case-Control Study. Eur J Contracept Reprod Health Care 1998,3(4):194-200.
16. Mathieu D, Kobeiter H, Maison P, Rahmouni A, Cherqui D, Zafrani ES, Dhumeaux D: Oral contraceptive use and focal nodular hyperplasia of the liver. Gastroenterology 2000,118(3):560-564.
17. Fukukura Y, Nakashima O, Kusaba A, Kage M, Kojiro M:Angioarchitecture and blood circulation in focal nodular hyperplasia of the liver. Journal of hepatology 1998, 29(3):470-475.
18. Langman G, Hall PD:Focal nodular hyperplasia with calcification and ossification. Pathology 2001,33(3):396-398.
19. De Gaetano AM, Gui B, Macis G, Manfredi R, Di Stasi C:Congenital absence of the portal vein associated with focal nodular hyperplasia in the liver in an adult woman: imaging and review of the literature. Abdominal imaging 2004,29(4):455-459.
20. Wanless IR, Terris B, Bioulac-Sage P:Focal hyperplasia(FH) of liver associated with localized hepatic vein thrombosis:a lesion with some features of'focal nodular hyperplasia'. Mod Pathol 2000,13:191.
21. Mindikoglu AL, Regev A, Levi JU, Casillas J, Schiff ER:Focal nodular hyperplasia in identical twins. The American journal of gastroenterology 2005,100(7):1616-1619.
22. Joyner BL, Jr., Levin TL, Goyal RK, Newman B:Focal nodular hyperplasia of the liver:a sequela of tumor therapy. Pediatric radiology 2005,35(12):1234-1239.
23. Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C:Focal nodular hyperplasia of the liver:a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. The American journal of surgical pathology 1999, 23(12):1441-1454.
24. Nakayama S, Kanbara Y, Nishimura T, Nishida N, Hanioka K, Morita M, Fujita M,
Sakurai K, Hayashi Y:Genome-wide microsatellite analysis of focal nodular hyperplasia:a strong tool for the differential diagnosis of non-neoplastic liver nodule from hepatocellular carcinoma. Journal of hepato-biliary-pancreatic surgery 2006, 13(5):416-420. 25. Baumhueter S, Mendel DB, Conley PB, Kuo CJ, Turk C, Graves MK, Edwards CA, Courtois G, Crabtree GR:HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Genes & development 1990, 4(3):372-379. 26. Cereghini S, Yaniv M, Cortese R:Hepatocyte dedifferentiation and extinction is accompanied by a block in the synthesis of mRNA coding for the transcription factor HNF1/LFB1. Embo J 1990,9(7):2257-2263. 27. Chouard T, Blumenfeld M, Bach I, Vandekerckhove J, Cereghini S, Yaniv M:A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. Nucleic acids research 1990,18(19):5853-5863. 28. Shiraishi K, Okita K, Kusano N, Harada T, Kondoh S, Okita S, Ryozawa S, Ohmura R, Noguchi T, Iida Y et al: A comparison of DNA copy number changes detected by
comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas. Oncology 2001,60(2):151-161.
29. Niketeghad F, Decker HJ, Caselmann WH, Lund P, Geissler F, Dienes HP, Schirmacher P:Frequent genomic imbalances suggest commonly altered tumour genes in human hepato carcinogenesis. British journal of cancer 2001,85(5):697-704.
30. Chen YJ, Chen PJ, Lee MC, Yeh SH, Hsu MT, Lin CH:Chromosomal analysis of hepatic adenoma and focal nodular hyperplasia by comparative genomic hybridization. Genes, chromosomes & cancer 2002,35(2):138-143.
31. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
32. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N et al: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science (New York, NY 1997, 277(5322):55-60.
33. Paradis V, Benzekri A, Dargere D, Bieche I, Laurendeau I, Vilgrain V, Belghiti J, Vidaud M, Degott C, Bedossa P:Telangiectatic focal nodular hyperplasia:a variant of hepatocellular adenoma. Gastroenterology 2004,126(5):1323-1329.
34. Paradis V, Bieche I, Dargere D, Laurendeau I, Nectoux J, Degott C, Belghiti J, Vidaud M, Bedossa P:A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia. Gastroenterology 2003,124(3):651-659.
35. Schlott T, Ahrens K, Ruschenburg I, Reimer S, Hartmann H, Droese M:Different gene expression of MDM2, GAGE-1,-2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. British journal of cancer 1999,80(1-2):73-78.
36. 王淑芳,苏勤,朱少君,刘节,胡灵芝,李东红：多发性子宫平滑肌瘤的克隆性.中华病理学杂志 2002,31：107-111.
37. Gilliland DG, Blanchard KL, Levy J, Perrin S, Bunn HF:Clonality in myeloproliferative disorders:analysis by means of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 1991,88(15):6848-6852.
38. Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW:Methylation of HpaⅡ and HhaⅠ sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. American journal of human genetics 1992,51(6):1229-1239.
39. Melenhorst JJ, Fibbe WE, Smits S, Willemze R, Landegent JE:Aplastic anaemia patients with clonal X-chromosome inactivation pattern in haemopoietic cells exhibit polyclonal TCRgamma and IgH gene rearrangements. British journal of haematology 1996,93(2):326-332.
40. Bannasch P, Schroder CH:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
41. Su Q, Benner A, Hofinann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
42. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31(1):126-133.
43. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
44. 初霞,苏勤,巩丽,张伟,王淑芳,朱少君,李爱宁,冯英明：慢性乙型肝炎和
肝硬化组织中变异肝细胞结节的克隆性.世界华人消化杂志 2005,13(8)：945-952.
45. 巩丽,张宏图,张伟,李爱宁,刘杉,孙耘田,刘贵秋,苏勤：克隆性分析技术在肝脏局灶性结节性增生诊断中的应用.世界华人消化杂志 2006,14(6)：568-575.
46. Bluteau O, Jeannot E, Bioulac-Sage P, Marques JM, Blanc JF, Bui H, Beaudoin JC, Franco D, Balabaud C, Laurent-Puig P et al: Bi-allelic inactivation of TCF1 in hepatic adenomas. Nature genetics 2002,32(2):312-315.
47. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J:Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol 2007, 13(19):2649-2654.
48. Mays ET, Christopherson WM, Barrows GH:Focal nodular hyperplasia of the liver. Possible relationship to oral contraceptives. American journal of clinical pathology 1974,61(6):735-746.
49. Laurent C, Trillaud H, Lepreux S, Balabaud C, Bioulac-Sage P:Association of adenoma and focal nodular hyperplasia:experience of a single French academic center. Comparative hepatology 2003,2(1):6.
50. Edmondson HA, Steiner PE:Primary carcinoma of the liver:a study of 100 cases among 48,900 necropsies. Cancer 1954,7(3):462-503.
51. Friedman LS, Gang DL, Hedberg SE, Isselbacher KJ:Simultaneous occurrence of hepatic adenoma and focal nodular hyperplasia:report of a case and review of the literature. Hepatology (Baltimore, Md 1984,4(3):536-540.
52. Grange JD, Guechot J, Legendre C, Giboudeau J, Darnis F, Poupon R:Liver adenoma and focal nodular hyperplasia in a man with high endogenous sex steroids. Gastroenterology 1987,93(6):1409-1413.
53. Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D:Association of focal nodular hyperplasia and hepatic hemangioma. Gastroenterology 1989,97(1):154-157.
54. Di Carlo I, Urrico GS, Ursino V, Russello D, Puleo S, Latteri F:Simultaneous occurrence of adenoma, focal nodular hyperplasia, and hemangioma of the liver:are they derived from a common origin? Journal of gastroenterology and hepatology 2003,18(2):227-230.
55. Saul SH, Titelbaum DS, Gansler TS, Varello M, Burke DR, Atkinson BF, Rosato EF: The fibrolamellar variant of hepatocellular carcinoma. Its association with focal nodular hyperplasia. Cancer 1987,60(12):3049-3055.
56. Vecchio FM, Fabiano A, Ghirlanda G, Manna R, Massi G:Fibrolamellar carcinoma of the liver:the malignant counterpart of focal nodular hyperplasia with oncocytic change. American journal of clinical pathology 1984,81(4):521-526.
57. Kellner U, Jacobsen A, Kellner A, Mantke R, Roessner A, Rocken C:Comparative genomic hybridization. Synchronous occurrence of focal nodular hyperplasia and hepatocellular carcinoma in the same liver is not based on common chromosomal aberrations. American journal of clinical pathology 2003,119(2):265-271.
58. Cucchetti A, Vivarelli M, De Ruvo N, Bellusci R, Cavallari A:Simultaneous presence of focal nodular hyperplasia and hepatocellular carcinoma:case report and review of the literature. Tumori 2003,89(4):434-436.
59. Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy PF,2nd:Hepatic adenoma and focal nodular hyperplasia:clinical, pathologic, and radiologic features. Gastroenterology 1983,84(5 Pt 1):994-1002.
1. Zender L, Xue W, Cordon-Cardo C, Hannon GJ, Lucito R, Powers S, Flemming P, Spector MS, Lowe SW:Generation and analysis of genetically defined liver carcinomas derived from bipotential liver progenitors. Cold Spring Harbor symposia on quantitative biology 2005,70:251-261.
2. Parkin DM, Bray F, Ferlay J, Pisani P:Global cancer statistics,2002. CA:a cancer journal for clinicians 2005,55(2):74-108.
3. Pisani P, Bray F, Parkin DM:Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. International journal of cancer 2002,97(1):72-81.
4. Montalto G, Cervello M, Giannitrapani L, Dantona F, Terranova A, Castagnetta LA: Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Annals of the New York Academy of Sciences 2002,963:13-20.
5. Macdonald GA:Pathogenesis of hepatocellular carcinoma. Clinics in liver disease 2001,5(1):69-85.
6. Aguayo A, Patt YZ:Liver cancer. Clinics in liver disease 2001,5(2):479-507.
7. Anthony PP, Vogel CL, Barker LF:Liver cell dysplasia:a premalignant condition. Journal of clinical pathology 1973,26(3):217-223.
8. Lee RG, Tsamandas AC, Demetris AJ:Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis:matched case-control study, pathological analysis, and pathogenetic hypothesis. Hepatology (Baltimore, Md 1997, 26(6):1415-1422.
9. Watanabe S, Okita K, Harada T, Kodama T, Numa Y, Takemoto T, Takahashi T: Morphologic studies of the liver cell dysplasia. Cancer 1983,51(12):2197-2205.
10. Libbrecht L, Craninx M, Nevens F, Desmet V, Roskams T:Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis. Histopathology 2001,39(1):66-73.
11. Gorla GR, Malhi H, Gupta S:Polyploidy associated with oxidative injury attenuates proliferative potential of cells. Journal of cell science 2001,114(Pt 16):2943-2951.
12. 苏勤：人肝细胞癌的癌前期病变.诊断病理学杂志2003,10：112-115.
13. Ganne-Carrie N, Chastang C, Chapel F, Munz C, Pateron D, Sibony M, Deny P, Trinchet JC, Callard P, Guettier C et al: Predictive score for the development of hepatocellular carcinoma and additional value of liver large cell dysplasia in Western patients with cirrhosis. Hepatology (Baltimore, Md 1996,23(5):1112-1118.
14. Donato MF, Arosio E, Del Ninno E, Ronchi G, Lampertico P, Morabito A, Balestrieri MR, Colombo M:High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity. Hepatology (Baltimore, Md 2001,34(3):523-528.
15. Aihara T, Noguchi S, Sasaki Y, Nakano H, Monden M, Imaoka S:Clonal analysis of precancerous lesion of hepatocellular carcinoma. Gastroenterology 1996, 111(2):455-461.
16. 苏勤,刘彦仿：乙型肝炎、肝硬变中癌前病变的形态学和免疫组织化学观察.第四军医大学学报1995,16(2)：85-88.
17. Okuda K:Hepatocellular carcinoma:recent progress. Hepatology (Baltimore, Md 1992,15(5):948-963.
18. Terminology of nodular hepatocellular lesions. International Working Party. Hepatology (Baltimore, Md 1995,22(3):983-993.
19. Bannasch P SC:Tumors and tumor-lik lesions of the liver and biliary tract: pathogenesis of primary liver tumors. In:MacSween RNM, Burt AD, Portmann BC et al. London:Churchill Livingstone; 2002.
20. Farber E, Sarma DS:Hepatocarcinogenesis:a dynamic cellular perspective. Laboratory investigation; a journal of technical methods and pathology 1987, 56(1):4-22.
21. Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Human hepatic preneoplasia:phenotypes and proliferation kinetics of foci and nodules of altered hepatocytes and their relationship to liver cell dysplasia. Virchows Arch 1997, 431(6):391-406.
22. Su Q, Zerban H, Otto G, Bannasch P:Cytokeratin expression is reduced in glycogenotic clear hepatocytes but increased in ground-glass cells in chronic human and woodchuck hepadnaviral infection. Hepatology (Baltimore, Md 1998, 28(2):347-359.
23. Su Q, Bannasch P:Relevance of hepatic preneoplasia for human hepatocarcinogenesis. Toxicologic pathology 2003,31(1):126-133.
24. Su Q, Schroder CH, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P:Expression of hepatitis B virus X protein in HBV-infected human livers and hepatocellular carcinomas. Hepatology (Baltimore, Md 1998,27(4):1109-1120.
25. Su Q, Liu YF, Zhang JF, Zhang SX, Li DF, Yang JJ:Expression of insulin-like growth factor Ⅱ in hepatitis B, cirrhosis and hepatocellular carcinoma:its relationship with hepatitis B virus antigen expression. Hepatology (Baltimore, Md 1994,20(4 Pt 1):788-799.
26. Su Q, Schroder CH, Otto G, Bannasch P:Overexpression of p53 protein is not directly related to hepatitis B x protein expression and is associated with neoplastic progression in hepatocellular carcinomas rather than hepatic preneoplasia. Mutation research 2000,462(2-3):365-380.
27. Henkler F, Waseem N, Golding MH, Alison MR, Koshy R:Mutant p53 but not hepatitis B virus X protein is present in hepatitis B virus-related human hepatocellular carcinoma. Cancer research 1995,55(24):6084-6091.
28. Anthony PP:Hepatocellular carcinoma:an overview. Histopathology 2001, 39(2):109-118.
29. Roncalli M, Bianchi P, Grimaldi GC, Ricci D, Laghi L, Maggioni M, Opocher E, Borzio M, Coggi G:Fractional allelic loss in non-end-stage cirrhosis:correlations with hepatocellular carcinoma development during follow-up. Hepatology (Baltimore, Md 2000,31(4):846-850.
30. Takaishi H, Kitamoto M, Takahashi S, Aikata H, Kawakami Y, Nakanishi T, Nakamura Y, Shimamoto F, Kajiyama G, Ide T:Precancerous hepatic nodules had significant levels of telomerase activity determined by sensitive quantitation using a hybridization protection assay. Cancer 2000,88(2):312-317.
31. Chuma M, Sakamoto M, Yamazaki K, Ohta T, Ohki M, Asaka M, Hirohashi S: Expression profiling in multistage hepatocarcinogenesis:identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology (Baltimore, Md 2003, 37(1):198-207.
32. Tiniakos DG, Brunt EM:Proliferating cell nuclear antigen and Ki-67 labeling in hepatocellular nodules:a comparative study. Liver 1999,19(1):58-68.
33. Libbrecht L, Desmet V, Van Damme B, Roskams T:The immunohistochemical phenotype of dysplastic foci in human liver:correlation with putative progenitor cells. Journal of hepatology 2000,33(1):76-84.
34. Kay A ME, Trepo C, Galibert F.:The HBV HBX gene expressed in E. coli is recognised by sera from hepatitis patients. EMBO J 1985,4(5):1287-1292.
35. Murakami S:Hepatitis B virus X protein:a multifunctional viral regulator. Journal of gastroenterology 2001,36(10):651-660.
36. Xu ZH, Zhao MJ, Li TP:p73beta inhibits transcriptional activities of enhancer I and X promoter in hepatitis B virus more efficiently than p73alpha. World J Gastroenterol 2002,8(6):1094-1097.
37. Su F, Theodosis CN, Schneider RJ:Role of NF-kappaB and myc proteins in apoptosis induced by hepatitis B virus HBx protein. Journal of virology 2001,75(1):215-225.
38. Lin Y, Nomura T, Yamashita T, Dorjsuren D, Tang H, Murakami S:The transactivation and p53-interacting functions of hepatitis B virus X protein are mutually interfering but distinct. Cancer research 1997,57(22):5137-5142.
39. Elmore LW, Hancock AR, Chang SF, Wang XW, Chang S, Callahan CP, Geller DA, Will H, Harris CC:Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proceedings of the National Academy of Sciences of the United States of America 1997,94(26):14707-14712.
40. Chen X, Ko LJ, Jayaraman L, Prives C:p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes & development 1996,10(19):2438-2451.
41. Ahn JY, Jung EY, Kwun HJ, Lee CW, Sung YC, Jang KL:Dual effects of hepatitis B virus X protein on the regulation of cell-cycle control depending on the status of cellular p53. The Journal of general virology 2002,83(Pt 11):2765-2772.
42. Park US, Park SK, Lee YI, Park JG, Lee YI:Hepatitis B virus-X protein upregulates the expression of p21wafl/cipl and prolongs G1-->S transition via a p53-independent pathway in human hepatoma cells. Oncogene 2000,19(30):3384-3394.
43. Shimazu T, Takada S, Ueno Y, Hayashi Y, Koike K:Post-transcriptional control of the level of mRNA by hepatitis B virus X gene in the transient expression system using human hepatic cells. Genes Cells 1998,3(7):477-484.
44. Ogden SK, Lee KC, Barton MC:Hepatitis B viral transactivator HBx alleviates p53-mediated repression of alpha-fetoprotein gene expression. The Journal of biological chemistry 2000,275(36):27806-27814.
45. Arbuthnot P, Capovilla A, Kew M:Putative role of hepatitis B virus X protein in hepatocarcinogenesis:effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. Journal of gastroenterology and hepatology 2000, 15(4):357-368.
46. 王兆文,彭志海,李克,裘国强,张益,顾炜：p16影响乙肝病毒相关性肝细胞肝癌的发生.中华病理学杂志2003,25：356-358.
47. Fukushima K, Ueno Y, Yamagiwa Y, Yamakawa M, Iwasaki T, Ishii M, Toyota T, Shimosegawa T:Correlation between p21(wafl) and p16(INK4a) expression in hepatocellular carcinoma. Hepatol Res 2001,20(1):52-67.
48. Becker SA, Lee TH, Butel JS, Slagle BL:Hepatitis B virus X protein interferes with cellular DNA repair. Journal of virology 1998,72(1):266-272.
49. Jia L, Wang XW, Harris CC:Hepatitis B virus X protein inhibits nucleotide excision repair. International journal of cancer 1999,80(6):875-879.
50. Capovilla A, Carmona S, Arbuthnot P:Hepatitis B virus X-protein binds damaged DNA and sensitizes liver cells to ultraviolet irradiation. Biochemical and biophysical research communications 1997,232(1):255-260.
51. Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A:Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proceedings of the National Academy of Sciences of the United States of America 1990,87(17):6599-6603.
52. Noda K, Yoshihara H, Suzuki K, Yamada Y, Kasahara A, Hayashi N, Fusamoto H, Kamada T:Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma--its relationship to alcohol drinking and the age of transfusion. Alcoholism, clinical and experimental research 1996,20(1 Suppl):95A-100A.
53. Bahnassi AA, Zekri AR, El-Houssini S, Mokhtar NM, Abdel-Aziz AO, Sherif GM, El-Mishad AM, Khaled HM:Hepatitis C virus-NS3P in relation to p53, p21waf, mdm2, p21-ras and c-erbB2 in hepatocarcinogenesis. Journal of gastroenterology and hepatology 2005,20(11):1731-1740.
54. Baek KH, Park HY, Kang CM, Kim SJ, Jeong SJ, Hong EK, Park JW, Sung YC, Suzuki T, Kim CM et al: Overexpression of hepatitis C virus NS5A protein induces chromosome instability via mitotic cell cycle dysregulation. Journal of molecular biology 2006,359(1):22-34.
55. Tung P RR, Fan ST, Wong J.:Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma.. Ann Surg 2000, 232:100.
56. NIH:National institutes of hearth consensus development conference panel statement:management of hepatitis C. Hepatology (Baltimore, Md 1997,26:2.
57. Lee YI, Lee S, Das GC, Park US, Park SM, Lee YI:Activation of the insulin-like growth factor Ⅱ transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma. Oncogene 2000,19(33):3717-3726.
58. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC:Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 1991,350(6317):377-378.
59. Hayashi H, Sugio K, Matsumata T, Adachi E, Urata K, Tanaka S, Sugimachi K:The mutation of codon 249 in the p53 gene is not specific in Japanese hepatocellular carcinoma. Liver 1993,13(5):279-281.
60. Bailey MA, Brunt EM:Hepatocellular carcinoma:predisposing conditions and precursor lesions. Gastroenterology clinics of North America 2002,31(2):641-662.
61. Perlmutter DH:Liver injury in alpha 1-antitrypsin deficiency. Clinics in liver disease 2000,4(2):387-408, ⅵ.
62. Sternlieb I:Wilson's disease. Clinics in liver disease 2000,4(1):229-239, ⅷ-ⅸ.
63. Issa JP:Aging, DNA methylation and cancer. Critical reviews in oncology/hematology 1999,32(1):31-43.
64. Huang J, Zhang X, Zhang M, Zhu JD, Zhang YL, Lin Y, Wang KS, Qi XF, Zhang Q, Liu GZ et al: Up-regulation of DLK1 as an imprinted gene could contribute to human hepatocellular carcinoma. Carcinogenesis 2007,28(5):1094-1103.
65. Shih YL, Shyu RY, Hsieh CB, Lai HC, Liu KY, Chu TY, Lin YW:Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer 2006,107(3):579-590.
66. Kondo Y, Kanai Y, Sakamoto M, Mizokami M, Ueda R, Hirohashi S:Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatellite instability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology (Baltimore, Md 2000, 32(5):970-979.
67. Su H, Zhao J, Xiong Y, Xu T, Zhou F, Yuan Y, Zhang Y, Zhuang SM:Large-scale analysis of the genetic and epigenetic alterations in hepatocellular carcinoma from Southeast China. Mutation research 2008,641(1-2):27-35.
68. Raidl M, Pirker C, Schulte-Hermann R, Aubele M, Kandioler-Eckersberger D, Wrba F, Micksche M, Berger W, Grasl-Kraupp B:Multiple chromosomal abnormalities in human liver (pre)neoplasia. Journal of hepatology 2004,40(4):660-668.
69. Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P:Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. British journal of cancer 2005,
92(5):935-941.
70. Yeh SH, Chen PJ, Shau WY, Chen YW, Lee PH, Chen JT, Chen DS:Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma. Gastroenterology 2001,121(3):699-709.
71. Mori T, Nomoto S, Koshikawa K, Fujii T, Sakai M, Nishikawa Y, Inoue S, Takeda S, Kaneko T, Nakao A:Decreased expression and frequent allelic inactivation of the RUNX3 gene at 1p36 in human hepato cellular carcinoma. Liver Int 2005, 25(2):380-388.
72. Sun M, Eshleman JR, Ferrell LD, Jacobs Q Sudilovsky EC, Tuthill R, Hussein MR, Sudilovsky O:An early lesion in hepatic carcinogenesis:loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region. Hepatology (Baltimore, Md 2001,33(6):1415-1424.
73. Riva P, Crosti F, Orzan F, Dalpra L, Mortini P, Parafioriti A, Pollo B, Fuhrman Conti A, Miozzo M, Larizza L:Mapping of candidate region for chordoma development to 1p36.13 by LOH analysis. International journal of cancer 2003,107(3):493-497.
74. De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC, Jirtle RL:Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor Ⅱ receptor locus in human hepatocellular tumors. Oncogene 1995,10(9):1725-1729.
75. Ozaki I, Mizuta T, Zhao G, Yotsumoto H, Hara T, Kajihara S, Hisatomi A, Sakai T, Yamamoto K:Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma. Cancer research 2000,60(22):6519-6525.
76. Park WS, Lee JH, Park JY, Jeong SW, Shin MS, Kim HS, Lee SK, Lee SN, Lee SH, Park CG et al:Genetic analysis of the liver putative tumor suppressor (LPTS) gene in hepatocellular carcinomas. Cancer letters 2002,178(2):199-207.
77. Wu X, Jia HL, Wang YF, Ren N, Ye QH, Sun HC, Wang L, Liu YK, Tang ZY, Qin LX: HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma. Oncogene 2006,25(12):1832-1840.
78. Nagai H, Emi M, Terada Y, Baba M, Shimizu M, Konishi N, Kaneko S, Kobayashi K, Yumoto Y, Ghazizadeh M et al:DNA alterations during multi-step development of human hepatocellular carcinomas revealed by laser capture microdissection. Hepatol Res 2003,26(3):199-208.
79. Anders RA, Yerian LM, Tretiakova M, Davison JM, Quigg RJ, Domer PH, Hoberg J, Hart J:cDNA microarray analysis of macroregenerative and dysplastic nodules in end-stage hepatitis C virus-induced cirrhosis. The American journal of pathology 2003, 162(3):991-1000.
80. Nam SW, Park JY, Ramasamy A, Shevade S, Islam A, Long PM, Park CK, Park SE, Kim SY, Lee SH et al: Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling. Hepatology (Baltimore, Md 2005, 42(4):809-818.
81. Llovet JM, Chen Y, Wurmbach E, Roayaie S, Fiel MI, Schwartz M, Thung SN, Khitrov G, Zhang W, Villanueva A et al: A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology 2006,131 (6):1758-1767.
82. Hayashi D:[Study on the expression of oncogene mRNA in hepatocellular carcinoma using in situ hybridization technique]. Nippon Geka Gakkai zasshi 1994, 95(11):814-822.
83. 林月珍,丁濂,陈晋彦：癌前变异肝细胞c-myc、N-ras mRNA的表达及其与分化的关系.中华肿瘤杂志1993,15(2)：97.
84. Niu ZS, Li BK, Wang M:Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues. World J Gastroenterol 2002,8(5):822-826.
85. Kekule AS, Lauer U, Meyer M, Caselmann WH, Hofschneider PH, Koshy R:The preS2/S region of integrated hepatitis B virus DNA encodes a transcriptional transactivator. Nature 1990,343(6257):457-461.
86. 郑杰,武忠弼,阮幼冰,等：二乙基亚硝胺诱发大鼠肝癌前病变中c-myc、N-ras和γ-GT酶表达的相关性研究.肿瘤1995,15(6)：462.
87. Santoni-Rugiu E, Nagy P, Jensen MR, Factor VM, Thorgeirsson SS:Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha. The American journal of pathology 1996, 149(2):407-428.
88. De Souza AT, Hankins GR, Washington MK, Orton TC, Jirtle RL:M6P/IGF2R gene is mutated in human hepatocellular carcinomas with loss of heterozygosity. Nature genetics 1995, 11(4):447-449.
89. Seo JH, Park BC:Expression of insulin-like growth factor II in chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. Gan to kagaku ryoho 1995,22 Suppl 3:292-307.
90. Cariani E, Dubois N, Lasserre C, Briand P, Brechot C:Insulin-like growth factor Ⅱ (IGF-II) mRNA expression during hepatocarcinogenesis in transgenic mice. Journal of hepatology 1991,13(2):220-226.
91. Lamas E, Le Bail B, Housset C, Boucher O, Brechot C:Localization of insulin-like growth factor-Ⅱ and hepatitis B virus mRNAs and proteins in human hepatocellular carcinomas. Laboratory investigation; a journal of technical methods and pathology 1991,64(1):98-104.
92. Yang D, Faris R, Hixson D, Affigne S, Rogler CE:Insulin-like growth factor II blocks apoptosis of N-myc2-expressing woodchuck liver epithelial cells. Journal of virology 1996,70(9):6260-6268.
93. 杨冬华,徐重,杨波,等：不同肝病患者肝细胞中胰岛素样生长因子及其受体的表达.中华医学杂志 1996,26(1)：50.
94. Hsia CC, Kleiner DE, Jr., Axiotis CA, Di Bisceglie A, Nomura AM, Stemmermann GN, Tabor E:Mutations of p53 gene in hepatocellular carcinoma:roles of hepatitis B virus and aflatoxin contamination in the diet. Journal of the National Cancer Institute 1992,84(21):1638-1641.
95. Teramoto T, Satonaka K, Kitazawa S, Fujimori T, Hayashi K, Maeda S:p53 gene abnormalities are closely related to hepatoviral infections and occur at a late stage of hepatocarcinogenesis. Cancer research 1994,54(1):231-235.
96. Ojanguren I, Ariza A, Castella EM, Fernandez-Vasalo A, Mate JL, Navas-Palacios JJ: p53 immunoreactivity in hepatocellular adenoma, focal nodular hyperplasia, cirrhosis and hepatocellular carcinoma. Histopathology 1995,26(1):63-68.
97. Livni N, Eid A, Ilan Y, Rivkind A, Rosenmann E, Blendis LM, Shouval D, Galun E: p53 expression in patients with cirrhosis with and without hepatocellular carcinoma. Cancer 1995,75(10):2420-2426.
98. Yuan BZ, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC:Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP. Cancer research 1998, 58(10):2196-2199.
99. Durkin ME, Yuan BZ, Thorgeirsson SS, Popescu NC:Gene structure, tissue expression, and linkage mapping of the mouse DLC-1 gene (Arhgap7). Gene 2002, 288(1-2):119-127.
100. Park SW, Durkin ME, Thorgeirsson SS, Popescu NC:DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma. International
journal of oncology 2003,23(1):133-137.
101. Plaumann M, Seitz S, Frege R, Estevez-Schwarz L, Scherneck S:Analysis of DLC-1 expression in human breast cancer. Journal of cancer research and clinical oncology 2003,129(6):349-354.
102. Ng 10, Liang ZD, Cao L, Lee TK:DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer research 2000,60(23):6581-6584.
103. Wong CM, Lee JM, Ching YP, Jin DY, Ng IO:Genetic and epigenetic alterations of DLC-1 gene in hepatocellular carcinoma. Cancer research 2003,63(22):7646-7651.
104. Zhou X, Thorgeirsson SS, Popescu NC:Restoration of DLC-1 gene expression induces apoptosis and inhibits both cell growth and tumorigenicity in human hepatocellular carcinoma cells. Oncogene 2004,23(6):1308-1313.
105. Piao Z, Park YN, Kim H, Park C:Clonality of large regenerative nodules in liver cirrhosis. Liver 1997,17(5):251-256.
106. Theise ND:Cirrhosis and hepatocellular neoplasia:more like cousins than like parent and child. Gastroenterology 1996, 111(2):526-528.
107. Gong L, Su Q, Zhang W, Li AN, Zhu SJ, Feng YM:Liver cell adenoma:a case report with clonal analysis and literature review. World J Gastroenterol 2006, 12(13):2125-2129.
108. Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, Bacq Y, Leteurtre E, Paradis V, Michalak S et al: Genotype-phenotype correlation in hepatocellular adenoma:new classification and relationship with HCC. Hepatology 2006,43(3):515-524.
109. Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E et al: A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996,380(6570):152-154.
110. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001,409(6822):860-921.
111. 张建军,安倩：微卫星与肿瘤.癌症2000,19(10)：948-950.
112. Bailey AD, Pavelitz T, Weiner AM:The microsatellite sequence (CT)n x (GA)n promotes stable chromosomal integration of large tandem arrays of functional human U2 small nuclear RNA genes. Molecular and cellular biology 1998,18(4):2262-2271.
113. 周晓东：微卫星不稳定性与肿瘤.国外医学肿瘤学分册1996,23：212-215.
114. Meloni R, Albanese V, Ravassard P, Treilhou F, Mallet J:A tetranucleotide polymorphic microsatellite, located in the first intron of the tyrosine hydroxylase gene, acts as a transcription regulatory element in vitro. Human molecular genetics 1998, 7(3):423-428.
115. Kashi Y, King D, Soller M:Simple sequence repeats as a source of quantitative genetic variation. Trends Genet 1997,13(2):74-78.
116. Gerber HP, Seipel K, Georgiev O, Hofferer M, Hug M, Rusconi S, Schaffner W: Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science (New York, NY 1994,263(5148):808-811.
117. Stallings RL:Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence:implications for human genetic diseases. Genomics 1994,21(1):116-121.
118. Sia EA, Jinks-Robertson S, Petes TD:Genetic control of microsatellite stability. Mutation research 1997,383(1):61-70.
119. Subramanian S, Mishra RK, Singh L:Genome-wide analysis of microsatellite repeats in humans:their abundance and density in specific genomic regions. Genome biology 2003,4(2):R13.
120. Jurka J, Pethiyagoda C:Simple repetitive DNA sequences from primates:compilation and analysis. Journal of molecular evolution 1995,40(2):120-126.
121. Beckman JS, Weber JL:Survey of human and rat microsatellites. Genomics 1992, 12(4):627-631.
122. Sheu JC, Lin YW, Chou HC, Huang GT, Lee HS, Lin YH, Huang SY, Chen CH, Wang JT, Lee PH et al:Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan. British journal of cancer 1999,80(3-4):468-476.
123. Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S et al:Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype. Cancer research 1997,57(10):1986-1990.
124. Piao Z, Park C, Park JH, Kim H:Allelotype analysis of hepatocellular carcinoma. International journal of cancer 1998,75(1):29-33.
125. 方嬿,李国辉,卓子兰：20例原发性肝癌实体瘤的细胞遗传学研究.中国优生与遗传杂志1996,4：34-37.
126. 王辉云,关新元,方嬿：肝癌染色体DNA拷贝数的变化及其与临床病理和预后的关系.癌症1999,18：509-513.
127. 李升平,王辉云,张昌卿,冯启胜,余杏娟,陈敏山,黄丽惜,黄平,郭荣平,林小军,张亚奇,李锦清,李国辉,曾益新：原发性肝癌全基因组杂合性缺失的研究.中华医学杂志 2000,80(8)：577-581.
128. Becker SA, Zhou YZ, Slagle BL:Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer research 1996, 56(21):5092-5097.
129. Piao Z, Kim H, Jeon BK, Lee WJ, Park C:Relationship between loss of heterozygosity of tumor suppressor genes and histologic differentiation in hepatocellular carcinoma. Cancer 1997,80(5):865-872.