摘要
[背景]
乳腺平坦型上皮不典型性(flat epithelial atypia, FEA)的特征是一到几层的轻度不典型管腔上皮细胞。导管内原位癌(dutal carcinoma in situ, DCIS)和浸润性导管癌非特殊型(invasive dutal carcinoma, not otherwise specified, IDC-NOS)的遗传学变化也可见于FEA,尽管发生的几率不一样。至今,FEA中miRNA的表达及其与DCIS和IDC的关联,尚未见报道。
[方法]
(1)从270例DCIS中选出51例含FEA的病例,根据形态学表现将其分为4级,Ⅰ、Ⅱ级为低分级,Ⅲ、Ⅳ级为高分级；根据与DCIS的位置关系将其分为两组,并进行ER, PR,α-SMA, p63, p53, bcl-2, Her-2, cyclinD1, Ki-67免疫组化染色。
(2)对15例同时存在正常乳腺,FEA和/或DCIS以及17例IDC-NOS病例行miRNA-21原位杂交(in situ hybridization, ISH)。同时,用免疫组化(immunohistochemistry, IHC)方法研究miR-21的靶基因PDCD4,TM1和PTEN的表达。
[结果]
(1)Ⅰ～Ⅳ级FEA分别为28、8、6和9例；与DCIS位于同一象限的24例,与DCIS位于不同象限的27例,且随着FEA分级从低到高,其与DCIS位于同一象限的比例逐渐增加(Ⅰ、Ⅱ、Ⅲ、Ⅳ级分别为28.6%、37.5%、66.7%、100%)。免疫组化结果：α-SMA和p63染色显示,FEA的肌上皮细胞明显受压变薄。其余各项免疫指标的阳性表达率分别为ER (62.8%), PR (54.9%), p53 (21.6%), bcl-2 (62.8%), Her-2 (15.7%), cyclinD1 (62.8%), Ki-67 (35.3%).低分级FEA、高分级FEA和DCIS三者比较,Her-2、cyclinD1和Ki-67的表达存在差异,高分级FEA和DCIS的Her-2、cyclinD1、Ki-67阳性率均明显高于低分级FEA,但高分级FEA和DCIS间无明显差别；在位置关系上,与DCIS位于同一象限的FEA、与DCIS位于不同象限的FEA和DCIS者比较,Her-2、cyclinD1和Ki-67的表达也存在差异,且与DCIS位于不同象限FEA的Her-2、cyclinD1、Ki-67阳性率均明显低于DCIS,但与DCIS位于同一象限FEA和DCIS间无明显差别。
(2)15例正常乳腺当中有2例,15例FEA当中有7例,12例DCIS当中有9例,17例IDC-NOS中有15例niR-21呈阳性表达。在12例同时存在正常乳腺,FEA及DCIS的病例中,我们发现有5例miR-21从正常乳腺到FEA进而到DCIS呈表达上升趋势。有3例FEA为阴性而DCIS为阳性；另外的3例FEA和DCIS均为miR-21阴性表达；最后一例全部三种成分(正常乳腺,FEA和DCIS) miR-21皆为阳性表达。总之,我们观察到miR-21的阳性表达率从正常乳腺到FEA,DCIS进而到IDC-NOS有逐步增加的趋势。IHC结果表示：PTEN表达强度在四种成分(正常乳腺,FEA, DCIS和IDC-NOS)中没有明显差异；胞浆中的PDCD4染色从正常乳腺到IDC-NOS逐步升高,而胞核中的PDCD4染色从正常乳腺到IDC-NOS却逐步下降。TM1染色从正常乳腺中的阳性表达下降到在多数DCIS和IDC-NOS中呈阴性表达。而在FEA中,TM1的染色表型和正常乳腺相似。
【结论】
(1)FEA分级越高,与DCIS的位置关系越密切。FEA(特别是高分级的、与DCIS位置关系密切的FEA)作为一种具有恶性潜能的交界性病变,具有一定的意义。
(2) miR-21从乳腺正常导管上皮到FEA, DCIS和IDC-NOS的上调表达与肿瘤发生的形态学演变呈平行变化趋势。我们没有观察到miR-21和先前报道的它的靶向基因之间明确的关系。
【背景】
与散发性乳腺癌和BRCA2相关的乳腺癌相比,BRCA1相关的乳腺癌有其独特的临床病理特征,DNA拷贝数的变化和基因表型特征。microRNA (miRNA)在一系列的生理病理学功能主面发挥重要作用,例如生长发育,增殖凋亡以及肿瘤形成等等。我们的研究目的是探索BRCA1相关的乳腺癌是否有其独特的miRNA表达谱特征。
【方法】
用miRNA microarray方法研究BRCA1相关和非相关乳腺癌的miRNA表型特征。本研究包括8例BRCA1相关乳腺癌,10例BRCA1/2非相关的散发性乳腺癌和6例正常乳腺(最后汇集成2个标本),比较不同类别标本的328个flagged miRNA表达的各自特点。
【结果】
鉴定出在BRCA1突变和非突变的乳腺癌中明显差异表达的miRNA亚群。并且,从中进一步选出一些可能在BRCA1通路中发挥一定作用的niRNA。
【结论】
层序聚类分析方法证实与BRCA1/2非突变的散发性乳腺癌相比较,BRCA1突变的乳腺癌有其独特的miRNA表达谱特征。
[Background]
Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast carcinoma, not otherwise specified (IDC-NOS) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA.
[Methods]
(1)51 cases of FEA were selected from 270 cases of DCIS with FEA components. The cases were divided into 4 grades and 2 groups, and immunohistochemical study for ER, PR,α-SMA, p63, p53, bcl-2, Her-2, cyclinD1 and Ki-67 was performed on these cases.
(2) We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC-NOS. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry.
[Results]
(1) The cases of gradeⅠ-Ⅳof FEA were 28,8,6 and 9, respectively. There were 24 cases of FEA located in the same quadrant with DCIS and 27 cases in the different quadrant. The proportion of FEA in the same quadrant with DCIS increased with the grade of FEA (gradeⅠ,Ⅱ,Ⅲ,Ⅳwere 28.6%,37.5%,66.7%,100%, respectively). Immunohistochemically, myoepithelial cells of FEA appeared attenuated stained with a-SMA and p63. The positive rate of FEA for ER, PR, p53, bcl-2, Her-2, cyclinD1 and Ki-67 were 62.8%,54.9%,21.6%,62.8%,15.7%,62.8% and 35.3%, respectively. There were significant difference in the expression of Her-2, cyclinDl and Ki-67 among low grade FEA, high grade FEA and DICS, and the positive rate of Her-2, cyclinD1 and Ki-67 were significantly higher in high grade FEA and DICS than in low grade FEA. There were significant difference in the expression of Her-2, cyclinD1 and Ki-67 among FEA in the same quadrant with DCIS, FEA in the different quadrant with DCIS and DICS, and the positive rate of Her-2, cyclinD1 and Ki-67 were significantly lower in FEA in the different quadrant with DCIS than in DCIS.
(2) Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC-NOS cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in 5 cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC-NOS. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC-NOS. Cytoplasmic staining of PDCD4 increased from normal to IDC-NOS, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC-NOS cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue.
[Conclusions]
(1) The position relation between FEA and DCIS is closer with the higher grade of FEA. We should take FEA, especially FEA which is high grade and adjacent to DCIS, as a precancerous lesion.
(2) Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC-NOS parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.
[Background]
BRCA1 associated breast cancer has its own distinctive clinical features, histopathologic character, copy number alterations and gene expression profiles in comparison with sporadic breast cancer and BRCA2 associated cancer. MicroRNAs (miRNAs) play an important role in a series of biopathological functions, such as growth, development, apoptosis, proliferation and carcinogenesis. We aimed to explore the miRNA expression profiles in BRCA1 associated cases compared with BRCA1 non-associated cases.
[Methods]
MiRNA microarray method was applied to investigate the miRNA expression profiles of BRCA1 associated and non-associated breast cancer cases. Eight BRCA1 mutation cases, ten BRCA1/2 non-mutation sporadic breast cancer cases and 6 normal breast cases (pooled into two samples) were included and compared with 328 flagged miRNAs in our study.
[Results]
A subgroup of miRNAs was identified between BRCA1 mutation cases and BRCA1 non-mutation cases. With the help of Targetscan software, certain miRNAs were further selected among them, which might play a potential role in BRCA1 pathway.
[Conclusions]
Compared with BRCA1/2 non-mutation sporadic breast cancer cases and normal cases, BRCA1 mutation cases show a distinctive miRNA expression profiles by hierarchical cluster analysis.
引文
1. Tavassoli FA DP:World Health Organization classification of tumors of pathology and genetics, tumors of the breast and female genital organs. Lyon:IARC Press; 2003.
2. Schnitt SJ:The diagnosis and management of pre-invasive breast disease:flat epithelial atypia--classification, pathologic features and clinical significance. Breast Cancer Res 2003,5:263-268.
3. Bijker N, Peterse JL, Duchateau L, Julien JP, Fentiman IS, Duval C et al.:Risk factors for recurrence and metastasis after breast-conserving therapy for ductal carcinoma-in-situ:analysis of European Organization for Research and Treatment of Cancer Trial 10853. J Clin Oncol 2001,19:2263-2271.
4. Eusebi V, Feudale E, Foschini MP, Micheli A, Conti A, Riva C et al.:Long-term follow-up of in situ carcinoma of the breast. Semin Diagn Pathol 1994,11:223-235.
5. Dabbs DJ, Carter G, Fudge M, Peng Y, Swalsky P, Finkelstein S:Molecular alterations in columnar cell lesions of the breast. Mod Pathol 2006,19:344-349.
6. Moinfar F, Man YG, Bratthauer GL, Ratschek M, Tavassoli FA:Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type ("clinging ductal carcinoma in situ"):a simulator of normal mammary epithelium. Cancer 2000,88: 2072-2081.
7. Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP et al.:Columnar cell lesions of the breast:the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol 2005,29:734-746.
8. Zhang B, Pan X, Cobb GP, Anderson TA:microRNAs as oncogenes and tumor suppressors. Dev Biol 2007,302:1-12.
9. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T:Identification of novel genes coding for small expressed RNAs. Science 2001,294:853-858.
10. Lau NC, Lim LP, Weinstein EG, Bartel DP:An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001,294:858-862.
11. Lee RC, Ambros V:An extensive class of small RNAs in Caenorhabditis elegans. Science 2001,294:862-864.
12. Lee RC, Feinbaum RL, Ambros V:The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993,75: 843-854.
13. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al.: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
14. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F et al.:A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006,103:2257-2261.
15. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007,282:14328-14336.
16. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008,283:1026-1033.
17. Chan JA, Krichevsky AM, Kosik KS:MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005,65:6029-6033.
18. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007,133:647-658.
19. Boecker W:Preneoplasia of the Breast:A New Conceptual Approach to Proliferative Breast Disease. Saunders;2006.
20. Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold JH et al.:Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 2007,110:1697-1707.
21. Raval GN, Bharadwaj S, Levine EA, Willingham MC. Geary RL, Kute T et al.: Loss of expression of tropomyosin-1, a novel class Ⅱ tumor suppressor that induces anoikis, in primary breast tumors. Oncogene 2003,22:6194-6203.
22. Tsutsui S, Inoue H, Yasuda K, Suzuki K, Higashi H, Era S et al.:Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology 2005,68:398-404.
23.龚西騟,孟刚,杨枫,等.乳腺平坦型上皮不典型病变的形态及免疫表型特征[J].临床与实验病理学杂志,2004,29：267-272.
24.付丽,付笑影,草间律,等.乳腺交界性病变不典型囊性导管的临床病理学特征[J].中华病理学杂志,2004,33：221-224.
25. Pegram MD, Finn RS, Arzoo K, et al. The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells[J]. Oncogene,1997,15:537-547.
26. Y Umekita, Y Ohi, Y Sagara, H Yoshida. Overexpression of cyclinDl predicts for poor prognosis in estrogen receptor-negative breast cancer patients[J]. Int J Cancer, 2002,98:415-418.
27. Carol D. Jones, Katherine H. Darnell, Roger A. Warnke, et al.cyclinD1/CyclinD3 ratio by real-time PCR improves specificity for the diagnosis of mantle cell lymphoma[J]. Mol Diagn,2004,6:84-89.
28. Muneyuki Masuda, Masumi Suzui, Ryuji Yasumatu, et al. Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclinDl Overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma[J]. Cancer Res,2002,62:3351-3355.
29. Oyama T, Maluf H, Koerner F, et al. A typical cystic lobules:an early stage in the formation of low-grade ductal carcinoma in situ[J]. Virchows Arch,1999,435: 413-421.
30. Moira Crosier, David Scott, Ronald G, et al. Differences in Ki-67 and c-erbB2 expression between screen-detected and true interval breast cancers[J]. Clin Cancer Res,1999,5:2682-2688.
31. Eusebi V, Feudale E, Foschini MP, Micheli A, Conti A, Riva C et al.:Long-term follow-up of in situ carcinoma of the breast. Semin Diagn Pathol 1994,11:223-235.
32. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G et al.: Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 2007,67:11612-11620.
33. Dabbs DJ, Carter G, Fudge M, Peng Y, Swalsky P, Finkelstein S:Molecular alterations in columnar cell lesions of the breast. Mod Pathol 2006,19:344-349.
34. Moinfar F, Man YG, Bratthauer GL, Ratschek M, Tavassoli FA:Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type ("clinging ductal carcinoma in situ"):a simulator of normal mammary epithelium. Cancer 2000,88: 2072-2081.
35. Simpson PT, Gale T, Reis-Filho JS, Jones C, Parry S, Sloane JP et al.:Columnar cell lesions of the breast:the missing link in breast cancer progression? A morphological and molecular analysis. Am J Surg Pathol 2005,29:734-746.
36. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007,282:14328-14336.
37. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008,283:1026-1033.
38. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH et al.: MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 2008,27:4373-4379.
39. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY:MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008,18:350-359.
40. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 2008,27:4373-4379.
41. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY:MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008,18:350-359.
42. Vazquez F, Sellers WR:The PTEN tumor suppressor protein:an antagonist of phosphoinositide 3-kinase signaling. Biochim Biophys Acta 2000,1470:M21-M35.
43. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007,133:647-658.
44. Zhu L, Loo WT, Louis WC:PTEN and VEGF:possible predictors for sentinel lymph node micro-metastasis in breast cancer. Biomed Pharmacother 2007,61: 558-561.
45. Bose S, Chandran S, Mirocha JM, Bose N:The Akt pathway in human breast cancer:a tissue-array-based analysis. Mod Pathol 2006,19:238-245.
46. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008,283:1026-1033.
47. Wen YH, Shi X, Chiriboga L, Matsahashi S, Yee H, Afonja O:Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep 2007,18: 1387-1393.
48. Mudduluru G, Medved F, Grobholz R, Jost C, Gruber A, Leupold JH et al.:Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 2007,110:1697-1707.
49. Bharadwaj S, Prasad GL:Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by promoter methylation in cancer cells. Cancer Lett 2002,183:205-213.
50. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 targets the tumor suppressor gene tropomyosin 1(TPM1). J Biol Chem 2007,282:14328-14336.
51. Talotta F, Cimmino A, Matarazzo MR, Casalino L, De Vita G, D'Esposito M et al.: An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation. Oncogene 2009,28:73-84.
1. Claus EB, Risch N, Thompson WD:Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 1991,48:232-242.
2. Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA:p53 mutations in BRCA1-associated familial breast cancer. Lancet 1997,350:638-639.
3. de Bock GH, Tollenaar RA, Papelard H, Cornelisse CJ, Devilee P, Van De Vijver MJ:Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients. Br J Cancer 2001,85: 1347-1350.
4. Karp SE, Tonin PN, Begin LR, Martinez JJ, Zhang JC, Pollak MN et al.:Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of breast carcinoma in Ashkenazi Jewish women. Cancer 1997,80:435-441.
5. Lakhani SR, Reis-Filho JS, Fulford L, Penault-Llorca F, van der Vijver M, Parry S et al.:Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005,11:5175-5180.
6. Musolino A, Bella MA, Bortesi B, Michiara M, Naldi N, Zanelli P et al.:BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer:a population-based study. Breast 2007,16:280-292.
7. Noguchi S, Kasugai T, Miki Y, Fukutomi T, Emi M, Nomizu T:Clinicopathologic analysis of B. Cancer 1999,85:2200-2205.
8. 't Veer LJ, Dai H, Van De Vijver MJ, He YD, Hart AA, Mao M et al.:Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002,415: 530-536.
9. Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al.: Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001,344: 539-548.
10. Kote-Jarai Z, Matthews L, Osorio A, Shanley S, Giddings I, Moreews F et al.: Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage. Clin Cancer Res 2006,12:3896-3901.
11. Melchor L, Honrado E, Garcia MJ, Alvarez S, Palacios J, Osorio A et al.:Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene 2008,27:3165-3175.
12. Sorlie T, Perou CM, Tibshirani R, Aas T. Geisler S, Johnsen H et al.:Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001,98:10869-10874.
13. Melchor L, Honrado E, Garcia MJ, Alvarez S, Palacios J, Osorio A et al.:Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene 2008,27:3165-3175.
14. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al.:Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003,100:8418-8423.
15. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T:Identification of novel genes coding for small expressed RNAs. Science 2001,294:853-858.
16. Lau NC, Lim LP, Weinstein EG, Bartel DP:An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001,294:858-862.
17. Lee RC, Feinbaum RL, Ambros V:The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993,75: 843-854.
18. Lee RC, Ambros V:An extensive class of small RNAs in Caenorhabditis elegans. Science 2001,294:862-864.
19. O'Hara SP, Mott JL, Splinter PL, Gores GJ, LaRusso NF:MicroRNAs:key modulators of posttranscriptional gene expression. Gastroenterology 2009,136: 17-25.
20. Hagen JW, Lai EC:microRNA control of cell-cell signaling during development and disease. Cell Cycle 2008,7:2327-2332.
21. Kedde M, Agami R:Interplay between microRNAs and RNA-binding proteins determines developmental processes. Cell Cycle 2008,7:899-903.
22. Kovalchuk O, Tryndyak VP, Montgomery B, Boyko A, Kutanzi K, Zemp F et al.: Estrogen-induced rat breast carcinogenesis is characterized by alterations in DNA methylation, histone modifications and aberrant microRNA expression. Cell Cycle 2007,6:2010-2018.
23. Mascaux C, Laes JF, Anthoine G, Haller A, Ninane V, Burny A et al.:Evolution of microRNA expression during human bronchial squamous carcinogenesis. Eur Respir J 2009,33:352-359.
24. Ren J, Jin P, Wang E, Marincola FM, Stroncek DF:MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells. J Transl Med 2009,7:20.
25. Wang Y, Lee CG:MicroRNA and cancer--focus on apoptosis. J Cell Mol Med 2009,13:12-23.
26. Li W, Xie L, He X, Li J, Tu K, Wei L et al.:Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer 2008, 123:1616-1622.
27. Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J et al.:Clinicopathological significance of microRNA-31,-143 and-145 expression in colorectal cancer. Dis Markers 2009,26:27-34.
28. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL et al.:MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA2008,14:2348-2360.
29. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H et al.:MiRNA expression in urothelial carcinomas:important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 2009,124:2236-2242.
30. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL et al.:MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 2008,14:2348-2360.
31. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW et al.: Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A 2008,105: 13021-13026.
32. Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ et al.: MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007,8:R214.
33. van der Hout AH. van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Bruggenwirth H et al.:A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2:application in a Dutch cancer clinic setting. Hum Mutat 2006, 27:654-666.
34. van der Hout AH. van den Ouweland AM, van der Luijt RB, Gille HJ, Bodmer D, Bruggenwirth H et al.:A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2:application in a Dutch cancer clinic setting. Hum Mutat 2006, 27:654-666.
35. Wang H, Ach RA, Curry B:Direct and sensitive miRNA profiling from low-input total RNA. RNA 2007,13:151-159.
36. Gibcus JH, Tan LP, Harms G, Schakel RN, de Jong D, Blokzijl T et al.:Hodgkin lymphoma cell lines are characterized by a specific miRNA expression profile. Neoplasia 2009,11:167-176.
37. Kiriakidou M, Nelson PT, Kouranov A, Fitziev P, Bouyioukos C, Mourelatos Z et al.:A combined computational-experimental approach predicts human microRNA targets. Genes Dev 2004,18:1165-1178.
38. Boyerinas B, Park SM, Shomron N, Hedegaard MM, Vinther J, Andersen JS et al.:Identification of let-7-regulated oncofetal genes. Cancer Res 2008,68: 2587-2591.
39. Hebert SS, Horre K, Nicolai L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN et al.:Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 2008,105:6415-6420.
40. Ma L, Teruya-Feldstein J, Weinberg RA:Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007,449:682-688.
41. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ et al.: MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A 2008,105: 5874-5878.
42. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E et al.: MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 2007,104:15805-15810.
43. Wu L, Belasco JG:Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Mol Cell Biol 2005,25: 9198-9208.
44. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC:Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 2007,282:1479-1486.
45. Korpal M, Lee ES, Hu G, Kang Y:The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 2008,283: 14910-14914.
46. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al.:MicroRNA expression profiles classify human cancers. Nature 2005,435:834-838.
47. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al.: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
48. Navarro A, Gaya A, Martinez A, Urbano-Ispizua A, Pons A, Balague O et al.: MicroRNA expression profiling in classic Hodgkin lymphoma. Blood 2008,111: 2825-2832.
49. Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H et al.:MiRNA expression in urothelial carcinomas:important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 2009,124:2236-2242.
50. Laios A, O'Toole S, Flavin R, Martin C, Kelly L, Ring M et al.:Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer 2008,7:35.
51. Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y et al.:Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat 2008.
52. Nass D, Rosenwald S, Meiri E. Gilad S, Tabibian-Keissar H, Schlosberg A et al.: MiR-92b and miR-9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors. Brain Pathol 2008.
53. Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y et al.:Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat 2008.
54. Jones SW, Watkins G, Le Good N, Roberts S, Murphy CL, Brockbank SM et al.: The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthritis Cartilage 2009,17: 464-472.
55. Lau P, Verrier JD, Nielsen JA, Johnson KR, Notterpek L, Hudson LD: Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 2008,28:11720-11730.
56. Ma L, Teruya-Feldstein J, Weinberg RA:Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007,449:682-688.
57. Negrini M, Calin GA:Breast cancer metastasis:a microRNA story. Breast Cancer Res 2008,10:203.
58. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P et al.:Micro-RNA profiling in kidney and bladder cancers. Urol Oncol 2007,25:387-392.
59. Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI:Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue. Clin Cancer Res 2008,14:2588-2592.
60. Park SY, Lee JH, Ha M, Nam JW, Kim VN:miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol 2009,16:23-29.
61. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ et al.: MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins. Proc Natl Acad Sci U S A 2008,105: 5874-5878.
62. Stamatopoulos B, Meuleman N, Haibe-Kains B, Saussoy P, Van den Neste E, Michaux L et al.:MicroRNA-29c and microRNA-223 downregulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood 2009.
63. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR:Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 2009,69:1279-1283.
64. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC:Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 2008.
65. Lin SL, Chiang A, Chang D, Ying SY:Loss of mir-146a function in hormone-refractory prostate cancer. RNA 2008,14:417-424.
66. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR:Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 2009,69:1279-1283.
67. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC:Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 2008.
68. Lin SL, Chiang A, Chang D, Ying SY:Loss of mir-146a function in hormone-refractory prostate cancer. RNA 2008,14:417-424.
69. Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C et al.:Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS ONE 2008,3:e2557.
70. Dixon-McIver A, East P, Mein CA, Cazier JB, Molloy G, Chaplin T et al.: Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS ONE 2008,3:e2141.
71. Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI:Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue. Clin Cancer Res 2008,14:2588-2592.
72. Agirre X, Jimenez-Velasco A, Jose-Eneriz E, Garate L, Bandres E, Cordeu L et al.:Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res 2008,6:1830-1840.
73. Veerla S. Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H et al.:MiRNA expression in urothelial carcinomas:important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer 2009,124:2236-2242.
74. Starita LM, Parvin JD:The multiple nuclear functions of BRCA1:transcription, ubiquitination and DNA repair. Curr Opin Cell Biol 2003,15:345-350.
75. Collins N, Kupfer GM:Molecular pathogenesis of Fanconi anemia. Int J Hematol 2005,82:176-183.
76. Welcsh PL, Owens KN, King MC:Insights into the functions of BRCA1 and BRCA2. Trends Genet 2000,16:69-74.
77. Collins N, Kupfer GM:Molecular pathogenesis of Fanconi anemia. Int J Hematol 2005,82:176-183.
78. Zhang J, Powell SN:The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res 2005,3:531-539.
79. Yamakuchi M, Ferlito M, Lowenstein CJ:miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 2008,105:13421-13426.
80. Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S et al.:p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 2009, 106:3207-3212.
81. Kumamoto K, Spillare EA, Fujita K, Horikawa I, Yamashita T, Appella E et al.: Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res 2008, 68:3193-3203.
82. Yamakuchi M, Ferlito M, Lowenstein CJ:miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A 2008,105:13421-13426.
83. Zhu JY, Pfuhl T, Motsch N, Barth S, Nicholls J, Grasser F et al.:Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas. J Virol 2009,83:3333-3341.
84. Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H:A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 2008,29:1963-1966.
85. Shen J, Ambrosone CB, Zhao H:Novel genetic variants in microRNA genes and familial breast cancer. Int J Cancer 2009,124:1178-1182.
86. Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al.: Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001,344: 539-548.
87. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al.:Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001,98:10869-10874.
88. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al.: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
89. Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK et al.: Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer 2006,5:24.
90. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G et al.: Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 2007,67:11612-11620.
91. Liu WH, Yeh SH, Lu CC, Yu SL, Chen HY, Lin CY et al.:MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 2009,136:683-693.
92. Pandey DP, Picard D:miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor{alpha}mRNA. Mol Cell Biol 2009.
93. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC:Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 2007,282:1479-1486.
94. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC:Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 2007,282:1479-1486.
95. Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H:miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 2008,68:5004-5008.
96. Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H:miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 2008,68:5004-5008.
97. Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X et al.:MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem 2008,283:31079-31086.
98. Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C et al.: MicroRNA signatures predict estrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res 2009,11:R27.
99. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al.: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
1. McPherson K, Steel CM, Dixon JM:ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 2000,321:624-628.
2. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K et al.: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006,295:2492-2502.
3. Payne SJ, Bowen RL, Jones JL, Wells CA:Predictive markers in breast cancer--the present. Histopathology 2008,52:82-90.
4. Claus EB, Risch N, Thompson WD:Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 1991,48:232-242.
5. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P et al.:Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998,62:676-689.
6. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T:Identification of novel genes coding for small expressed RNAs. Science 2001,294:853-858.
7. Lee RC, Feinbaum RL, Ambros V:The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993,75: 843-854.
8. Lau NC, Lim LP, Weinstein EG, Bartel DP:An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001,294: 858-862.
9. Lee RC, Ambros V:An extensive class of small RNAs in Caenorhabditis elegans. Science 2001,294:862-864.
10. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E et al.:Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2002,99: 15524-15529.
11. Tam W, Hughes SH, Hayward WS, Besmer P:Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol 2002,76:4275-4286.
12. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT:c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005,435:839-843.
13. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H et al.: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004,64: 3753-3756.
14. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D et al.:MicroRNA expression profiles classify human cancers. Nature 2005,435:834-838.
15. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S et al.: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005,65:7065-7070.
16. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F et al.:A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006,103:2257-2261.
17. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY:miR-21-mediated tumor growth. Oncogene 2007,26:2799-2803.
18. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G et al.:Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 2007,67:11612-11620.
19. O'Hara AJ, Vahrson W, Dittmer DP:Gene alteration and precursor and mature microRNA transcription changes contribute to the miRNA signature of primary effusion lymphoma. Blood 2008,111:2347-2353.
20. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T: MicroRNA expression profiling in prostate cancer. Cancer Res 2007,67: 6130-6135.
21. Lamy P, Andersen CL, Dyrskjot L, Torring N, Orntoft T, Wiuf C:Are microRNAs located in genomic regions associated with cancer? Br J Cancer 2006,95:1415-1418.
22. Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A et al.: microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A 2006,103:9136-9141.
23. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC:Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res 2006,66: 1277-1281.
24. Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK et al.: Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer 2006,5:24.
25. Blenkiron C, Goldstein LD, Thome NP, Spiteri I, Chin SF, Dunning MJ et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007.8:R214.
26. Huang GL, Zhang XH, Guo GL, Huang KT, Yang KY, Shen X et al.:Clinical significance of miR-21 expression in breast cancer:SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma. Oncol Rep 2009,21: 673-679.
27. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD et al.: Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008,451:147-152.
28. Ma L, Teruya-Feldstein J, Weinberg RA:Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007,449:682-688.
29. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C et al.:let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007,131:1109-1123.
30. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan XY et al.: AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 1997,277:965-968.
31. Torres-Arzayus MI, Font de Mora J, Yuan J, Vazquez F, Bronson R, Rue M et al.:High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 2004,6:263-274.
32. Louie MC, Zou JX, Rabinovich A, Chen HW:ACTR/AIB1 functions as an E2F1 coactivator to promote breast cancer cell proliferation and antiestrogen resistance. Mol Cell Biol 2004,24:5157-5171.
33. Hossain A, Kuo MT, Saunders GF:Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 2006,26: 8191-8201.
34. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY:MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008,18:350-359.
35. Zhu S, Si ML, Wu H, Mo YY:MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007,282:14328-14336.
36. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH: Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008,283:1026-1033.
37. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007.133:647-658.
38. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH et al.: MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 2008,27:4373-4379.
39. Yang Y, Chaerkady R, Beer MA, Mendell JT, Pandey A:Identification of miR-21 targets in breast cancer cells using a quantitative proteomic approach. Proteomics 2009,9:1374-1384.
40. Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T:MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 2006,66:9090-9098.
41. Dutta KK, Zhong Y, Liu YT, Yamada T, Akatsuka S. Hu Q et al.:Association of microRNA-34a overexpression with proliferation is cell type-dependent. Cancer Sci 2007,98:1845-1852.
42. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC:Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 2007,282:1479-1486.
43. Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC:Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 2008.
44. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR:Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 2009,69:1279-1283.
45. Hurteau GJ, Carlson JA, Spivack SD, Brock GJ:Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res 2007,67:7972-7976.
46. Wu H, Zhu S, Mo YY:Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res 2009.
47. Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T et al.: microRNA-205 regulates HER3 in human breast cancer. Cancer Res 2009,69: 2195-2200.
48. Adams BD, Furneaux H, White BA:The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Mol Endocrinol 2007,21:1132-1147.
49. Zhao JJ, Lin J, Yang H, Kong W, He L, Ma X et al.:MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem 2008,283:31079-31086.
50. Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL et al.: MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 2008,283:29897-29903.
51. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S et al.:The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008,10:202-210.
1. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B et al.: Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990,250:1684-1689.
2. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al.:A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994,266:66-71.
3. Neuhausen SL, Marshall CJ:Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds. Cancer Res 1994,54:6069-6072.
4. Smith SA, Easton DF, Evans DG, Ponder BA:Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nat Genet 1992,2:128-131.
5. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J et al.: Identification of the breast cancer susceptibility gene BRCA2. Nature 1995,378: 789-792.
6. Collins N, McManus R, Wooster R, Mangion J, Seal S, Lakhani SR et al.: Consistent loss of the wild type allele in breast cancers from a family linked to the BRCA2 gene on chromosome 13q12-13. Oncogene 1995,10:1673-1675.
7. Chen JJ, Silver D, Cantor S, Livingston DM, Scully R:BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res 1999, 59:1752s-1756s.
8. Honrado E, Benitez J, Palacios J:The molecular pathology of hereditary breast cancer:genetic testing and therapeutic implications. Mod Pathol 2005,18: 1305-1320.
9. Cleton-Jansen AM, Collins N, Lakhani SR, Weissenbach J, Devilee P, Cornelisse CJ et al.:Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13. Br J Cancer 1995,72:1241-1244.
10. Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian S et al.:BRCA1 mutations in primary breast and ovarian carcinomas. Science 1994, 266:120-122.
11. Wilson CA, Ramos L, Villasenor MR, Anders KH, Press MF, Clarke K et al.: Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 1999,21:236-240.
12. Ford D, Easton DF, Peto J:Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995,57: 1457-1462.
13. Ford D, Easton DF, Peto J:Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995,57: 1457-1462.
14. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B et al.: Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990,250:1684-1689.
15. Easton DF, Bishop DT, Ford D, Crockford GP:Genetic linkage analysis in familial breast and ovarian cancer:results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1993,52:678-701.
16. Malone KE, Daling JR, Neal C, Suter NM, O'Brien C, Cushing-Haugen K et al.: Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 2000,88:1393-1402.
17. Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res 2006,66:8297-8308.
18. Kelly K.Hunt, Geoffrey L.Robb, Eric A.Strom, Naoto T.Ueno:Breast Cancer, second edition (MD Anderson Cancer Care Series),2nd Edition edn. Springer; 2001.
19. Struewing JP, Abeliovich D, Peretz T, Avishai N, Kaback MM, Collins FS et al.: The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 1995,11:198-200.
20. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M et al.: The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 1997,336:1401-1408.
21. Roa BB, Boyd AA, Volcik K, Richards CS:Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 1996,14: 185-187.
22. Oddoux C, Struewing JP, Clayton CM, Neuhausen S, Brody LC, Kaback M et al.:The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet 1996,14:188-190.
23. Verhoog LC, van den Ouweland AM, Berns E, Veghel-Plandsoen MM, van Staveren IL, Wagner A et al.:Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. Eur J Cancer 2001,37:2082-2090.
24. Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R. Drusedau M et al. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet 1997,17:341-345.
25. Neuhausen SL, Godwin AK, Gershoni-Baruch R, Schubert E, Garber J, Stoppa-Lyonnet D et al.:Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families:results of an international study. Am J Hum Genet 1998,62:1381-1388.
26. Noguchi S, Kasugai T, Miki Y, Fukutomi T, Emi M, Nomizu T: Clinicopathologic analysis of B. Cancer 1999,85:2200-2205.
27. Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L et al.:The pathology of familial breast cancer:predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 2002, 20:2310-2318.
28. Robson M, Rajan P, Rosen PP, Gilewski T, Hirschaut Y, Pressman P et al.: BRCA-associated breast cancer:absence of a characteristic immunophenotype. Cancer Res 1998,58:1839-1842.
29. Armes JE, Egan AJ, Southey MC, Dite GS, McCredie MR, Giles GG et al.:The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations:a population-based study. Cancer 1998,83:2335-2345.
30. Armes JE, Egan AJ, Southey MC, Dite GS, McCredie MR, Giles GG et al.:The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations:a population-based study. Cancer 1998,83:2335-2345.
31. Pathology of familial breast cancer:differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage Consortium. Lancet 1997,349:1505-1510.
32. Shrivastav M, De Haro LP, Nickoloff JA:Regulation of DNA double-strand break repair pathway choice. Cell Res 2008,18:134-147.
33. Sonoda E, Hochegger H, Saberi A, Taniguchi Y, Takeda S:Differential usage of non-homologous end-joining and homologous recombination in double strand break repair. DNA Repair (Amst) 2006,5:1021-1029.
34. Wang T, Waters CT, Rothman AM, Jakins TJ, Romisch K, Trump D: Intracellular retention of mutant retinoschisin is the pathological mechanism underlying X-linked retinoschisis. Hum Mol Genet 2002,11:3097-3105.
35. Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J et al.:Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 1997,88:265-275.
36. Deng CX, Wang RH:Roles of BRCA1 in DNA damage repair:a link between development and cancer. Hum Mol Genet 2003,12 Spec No 1:R113-R123.
37. Moynahan ME, Cui TY, Jasin M:Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brcal mutation. Cancer Res 2001,61:4842-4850.
38. Moynahan ME, Chiu JW, Koller BH, Jasin M:Brcal controls homology-directed DNA repair. Mol Cell 1999,4:511-518.
39. Wang H, Zeng ZC, Bui TA, DiBiase SJ, Qin W, Xia F et al.:Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2. Cancer Res 2001,61: 270-277.
40. Treszezamsky AD, Kachnic LA, Feng Z, Zhang J, Tokadjian C, Powell SN:B. Cancer Res 2007,67:7078-7081.
41. Simons AM, Horwitz AA, Starita LM, Griffin K, Williams RS, Glover JN et al.: BRCA1 DNA-binding activity is stimulated by BARD1. Cancer Res 2006,66: 2012-2018.
42. Lee SA, Roques C, Magwood AC, Masson JY, Baker MD:Recovery of deficient homologous recombination in Brca2-depleted mouse cells by wild-type Rad51 expression. DNA Repair (Amst) 2009,8:170-181.
43. Moynahan ME, Chiu JW, Koller BH, Jasin M:Brcal controls homology-directed DNA repair. Mol Cell 1999,4:511-518.
44. Merel P, Prieur A, Pfeiffer P, Delattre O:Absence of major defects in non-homologous DNA end joining in human breast cancer cell lines. Oncogene 2002,21:5654-5659.
45. Wang HC, Chou WC, Shieh SY, Shen CY:Ataxia telangiectasia mutated and checkpoint kinase 2 regulate BRCA1 to promote the fidelity of DNA end-joining. Cancer Res 2006,66:1391-1400.
46. Bau DT, Fu YP, Chen ST, Cheng TC, Yu JC, Wu PE et al.:Breast cancer risk and the DNA double-strand break end-joining capacity of nonhomologous end-joining genes are affected by BRCA1. Cancer Res 2004,64:5013-5019.
47. Fu YP, Yu JC, Cheng TC, Lou MA, Hsu GC, Wu CY et al.:Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes:a multigenic study on cancer susceptibility. Cancer Res 2003,63: 2440-2446.
48. Dudasova Z, Dudas A, Chovanec M:Non-homologous end-joining factors of Saccharomyces cerevisiae. FEMS Microbiol Rev 2004,28:581-601.
49. Manolis KG, Nimmo ER, Hartsuiker E, Carr AM, Jeggo PA, Allshire RC:Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. EMBO J 2001,20:210-221.
50. Tauchi H, Kobayashi J, Morishima K, van Gent DC, Shiraishi T, Verkaik NS et al.:Nbsl is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature 2002,420:93-98.
51. Zhuang J, Zhang J, Willers H, Wang H, Chung JH, van Gent DC et al.: Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of nonhomologous end-joining. Cancer Res 2006,66:1401-1408.
52. Brodie SG, Xu X, Qiao W, Li WM, Cao L, Deng CX:Multiple genetic changes are associated with mammary tumorigenesis in Brcal conditional knockout mice. Oncogene 2001,20:7514-7523.
53. Weaver Z, Montagna C, Xu X, Howard T, Gadina M, Brodie SG et al.: Mammary tumors in mice conditionally mutant for Brcal exhibit gross genomic instability and centrosome amplification yet display a recurring distribution of genomic imbalances that is similar to human breast cancer. Oncogene 2002,21: 5097-5107.
54. Deng CX:Tumorigenesis as a consequence of genetic instability in Brcal mutant mice. Mutat Res 2001,477:183-189.
55. Fan W, Jin S, Tong T, Zhao H, Fan F, Antinore MJ et al.:BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs. J Biol Chem 2002,277:8061-8067.
56. Takimoto R, MacLachlan TK, Dicker DT, Niitsu Y, Mori T, el Deiry WS: BRCA1 transcriptionally regulates damaged DNA binding protein (DDB2) in the DNA repair response following UV-irradiation. Cancer Biol Ther 2002,1: 177-186.
57. Hartman AR, Ford JM:BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair. Nat Genet 2002,32:180-184.
58. Chen GC, Guan LS, Yu JH, Li GC, Choi Kim HR, Wang ZY:Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCAl. Biochem Biophys Res Commun 2001,284:507-514.
59. Kleiman FE, Wu-Baer F, Fonseca D, Kaneko S, Baer R, Manley JL BRCA1/BARD1 inhibition of mRNA 3'processing involves targeted degradation of RNA polymerase Ⅱ. Genes Dev 2005,19:1227-1237.
60. Abramovitch S, Werner H:Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene. Horm Metab Res 2003,35:758-762.
61. Preobrazhenska O, Yakymovych M, Kanamoto T, Yakymovych I, Stoika R, Heldin CH et al.:BRCA2 and Smad3 synergize in regulation of gene transcription. Oncogene 2002,21:5660-5664.
62. Xu B, O'Donnell AH, Kim ST, Kastan MB:Phosphorylation of serine 1387 in Brcal is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res 2002,62:4588-4591.
63. Mullan PB, Quinn JE, Gilmore PM, McWilliams S, Andrews H, Gervin C et al.: BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule agents. Oncogene 2001,20:6123-6131.
64. Yan Y, Spieker RS, Kim M, Stoeger SM, Cowan KH:BRCA1-mediated G2/M cell cycle arrest requires ERK1/2 kinase activation. Oncogene 2005,24: 3285-3296.
65. Marmorstein LY, Kinev AV, Chan GK, Bochar DA, Beniya H, Epstein JA et al.: A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression. Cell 2001,104:247-257.
66. Jonsson G, Naylor TL, Vallon-Christersson J, Staaf J, Huang J, Ward MR et al. Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization. Cancer Res 2005,65:7612-7621.
67. Joosse SA, van Beers EH, Tielen IH, Horlings H, Peterse JL, Hoogerbrugge N et al.:Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH. Breast Cancer Res Treat 2008.
68. Joosse SA, van Beers EH, Tielen IH, Horlings H, Peterse JL, Hoogerbrugge N et al.:Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH. Breast Cancer Res Treat 2008.
69. van Beers EH, van Welsem T, Wessels LF, Li Y, Oldenburg RA, Devilee P et al.: Comparative genomic hybridization profiles in human BRCA1 and BRCA2 breast tumors highlight differential sets of genomic aberrations. Cancer Res 2005,65:822-827.
70. Jonsson G, Naylor TL, Vallon-Christersson J, Staaf J, Huang J, Ward MR et al.: Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization. Cancer Res 2005,65:7612-7621.
71. Jonsson G, Naylor TL, Vallon-Christersson J, Staaf J, Huang J, Ward MR et al.: Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization. Cancer Res 2005,65:7612-7621.
72. Joosse SA, van Beers EH, Tielen IH, Horlings H, Peterse JL, Hoogerbrugge N et al.:Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH. Breast Cancer Res Treat 2008.
73. van Beers EH, van Welsem T, Wessels LF, Li Y, Oldenburg RA, Devilee P et al.: Comparative genomic hybridization profiles in human BRCA1 and BRCA2 breast tumors highlight differential sets of genomic aberrations. Cancer Res 2005,65:822-827.
74. Wessels LF, van Welsem T, Hart AA, van't Veer LJ, Reinders MJ, Nederlof PM: Molecular classification of breast carcinomas by comparative genomic hybridization:a specific somatic genetic profile for BRCA1 tumors. Cancer Res 2002,62:7110-7117.
75. Bergamaschi A. Kim YH, Wang P, Sorlie T, Hernandez-Boussard T, Lonning PE et al.:Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer 2006,45:1033-1040.
76. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al.:Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003,100:8418-8423.
77. Melchor L, Honrado E, Garcia MJ, Alvarez S, Palacios J, Osorio A et al.: Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene 2008,27: 3165-3175.
78. Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL et al.: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006,10:529-541.
79. Bergamaschi A, Kim YH, Wang P, Sorlie T, Hernandez-Boussard T, Lonning PE et al.:Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer 2006,45:1033-1040.
80. Bergamaschi A, Kim YH, Wang P, Sorlie T, Hernandez-Boussard T, Lonning PE et al.:Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer 2006,45:1033-1040.
81. Melchor L, Honrado E, Garcia MJ, Alvarez S, Palacios J, Osorio A et al.: Distinct genomic aberration patterns are found in familial breast cancer associated with different immunohistochemical subtypes. Oncogene 2008,27: 3165-3175.
82. Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL et al.: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006,10:529-541.
83. Tan DS, Marchio C, Reis-Filho JS:Hereditary breast cancer:from molecular pathology to tailored therapies. J Clin Pathol 2008,61:1073-1082.
84. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al.: Molecular portraits of human breast tumours. Nature 2000,406:747-752.
85. Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al. Gene-expression profiles in hereditary breast cancer. N Engl J Med 2001,344: 539-548.
86. Kote-Jarai Z, Matthews L, Osorio A, Shanley S, Giddings I, Moreews F et al.: Accurate prediction of BRCA1 and BRCA2 heterozygous genotype using expression profiling after induced DNA damage. Clin Cancer Res 2006,12: 3896-3901.
87.'t Veer LJ, Dai H, Van De Vijver MJ, He YD, Hart AA, Mao M et al.:Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002, 415:530-536.
88. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al.:Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003,100:8418-8423.
89. Tapia T, Smalley SV, Kohen P, Munoz A, Solis LM, Corvalan A et al.:Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors. Epigenetics 2008,3:157-163.
90. Alvarez S, Diaz-Uriarte R, Osorio A, Barroso A, Melchor L, Paz MF et al.:A predictor based on the somatic genomic changes of the BRCA1/BRCA2 breast cancer tumors identifies the non-BRCA1/BRCA2 tumors with BRCA1 promoter hypermethylation. Clin Cancer Res 2005,11:1146-1153.
91. Miyamoto K, Fukutomi T, Asada K, Wakazono K, Tsuda H, Asahara T et al. Promoter hypermethylation and post-transcriptional mechanisms for reduced BRCA1 immunoreactivity in sporadic human breast cancers. Jpn J Clin Oncol 2002,32:79-84.
92. Rice JC, Ozcelik H, Maxeiner P, Andrulis I, Futscher BW:Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis 2000,21:1761-1765.
93. Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S et al.:p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A 2009,106:3207-3212.
94. Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H:A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 2008,29:1963-1966.
95. Shen J, Ambrosone CB, Zhao H:Novel genetic variants in microRNA genes and familial breast cancer. Int J Cancer 2009,124:1178-1182.
96. Zhu JY, Pfuhl T, Motsch N, Barth S, Nicholls J, Grasser F et al.:Identification of novel Epstein-Barr virus microRNA genes from nasopharyngeal carcinomas. J Virol 2009,83:3333-3341.
97. Ashworth A:Drug resistance caused by reversion mutation. Cancer Res 2008, 68:10021-10023.
98. Tutt A, Ashworth A:Can genetic testing guide treatment in breast cancer? Eur J Cancer 2008,44:2774-2780.
99. Ashworth A:A synthetic lethal therapeutic approach:poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 2008,26:3785-3790.