少突星形细胞瘤组织形态异质性与分子遗传学的研究
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摘要
研究背景：少突星形细胞瘤是最常见的混合性胶质瘤，由两种不同的肿瘤细胞组成，组织形态上分别与弥漫性星形细胞瘤和少突胶质瘤中的肿瘤细胞相似。由于这一形态学的异质性，在进行临床病理诊断时，很容易将该肿瘤描述为弥漫性星形细胞瘤或是单纯的少突胶质瘤。近些年来，正确诊断少突胶质瘤及少突星形细胞瘤对临床工作的影响越来越受到人们的重视。因为相对于星形细胞瘤来说，大多数少突胶质瘤患者对放、化疗敏感，生存期也较长。少突胶质瘤中，1号染色体短臂及19号染色体长臂的杂合性缺失(LOH 1p／19q)是其特征性的分子改变，与放、化疗的敏感性及较好的预后直接相关。而弥漫性星形细胞瘤很少有LOH 1p／19q，但具有特征性的17号染色体短臂的杂合性缺失(LOH 17p)或是TP53基因突变。目前，就有关少突星形细胞瘤的起源问题存在两种不同的观点，一种认为少突星形细胞瘤为单克隆起源，与单纯的少突胶质瘤同源，而另一种则认为少突星形细胞瘤存在两种遗传学亚型，一种与星形细胞瘤同源，另一种与少突胶质瘤同源。
目的：探讨少突星形细胞瘤中，组织形态炯异的两种肿瘤细胞成分(星形细胞部分与少突胶质部分)是否具有不同的分子遗传学改变。
方法：选择11例临床确诊的WHOⅡ级少突星形细胞瘤患者，其中二
Background: Oligoastrocytomas are glial tumors composed of a mixture of two distinct neoplastic cell types, morphologically corresponding to oligodendrogliomas and astrocytomas. These two different cell types coexist either separately in different areas of the tumor, or intermingled within the same areas of the tumor. Due to this heterogeneous morphology of oligoastrocytoma, the histopathological diagnosis is subjective and can easily be interpreted to be diffuse astrocytomas or pure oligodendrogliomas. The clinical impact of correct diagnosis of oligodendrogliomas as well as oligoastrocytomas has become clear during recent years. In contrast to astrocytomas, most patients with oligodendrogliomas are responsive to chemotherapy and have a longer overall survival. Somatic deletions on the short arm of chromosome 1 and the long arm of chromosome 19 (LOH 1p and LOH 19q) were shown to be directly associated with the chemosensitivity of the tumor, and are at present used as a molecular guide in the
目的：探讨少突星形细胞瘤中，组织形态炯异的两种肿瘤细胞成分(星形细胞部分与少突胶质部分)是否具有不同的分子遗传学改变。
方法：选择11例临床确诊的WHOⅡ级少突星形细胞瘤患者，其中二
Background: Oligoastrocytomas are glial tumors composed of a mixture of two distinct neoplastic cell types, morphologically corresponding to oligodendrogliomas and astrocytomas. These two different cell types coexist either separately in different areas of the tumor, or intermingled within the same areas of the tumor. Due to this heterogeneous morphology of oligoastrocytoma, the histopathological diagnosis is subjective and can easily be interpreted to be diffuse astrocytomas or pure oligodendrogliomas. The clinical impact of correct diagnosis of oligodendrogliomas as well as oligoastrocytomas has become clear during recent years. In contrast to astrocytomas, most patients with oligodendrogliomas are responsive to chemotherapy and have a longer overall survival. Somatic deletions on the short arm of chromosome 1 and the long arm of chromosome 19 (LOH 1p and LOH 19q) were shown to be directly associated with the chemosensitivity of the tumor, and are at present used as a molecular guide in the
引文
1. Surawicz TS, McCarthy BJ, Kupelian V, Jukich PJ, Bruner JM, Davis FG Descriptive epidemiology of primarybrain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990 - 1994. Neuro-oncol 1999,1:14 - 25.
2. Miller RW, Young JL, Novakovic B Childhood cancer. Cancer 1995, 75:395 - 405.
3. Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, Linet MS Cancer surveillance series [corrected]: brain and other central nervous system cancers:recent trends in incidence and mortality. J Natl Cancer Inst 1999, 91:1382-1390.
4. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
5. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
6. Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2nd ed. Lyon, France: IARC Press; World Health Organization Classification of Tumours. 2000.
7. Perry A.Oligodendroglial neoplasms: current concepts, misconceptions, and folklore. Adv Anat Pathol. 2001, 8:183-199.
8. .Burger PC. What is an oligodendroglioma? Brain Pathol. 2002; 12:257-259.
9. Bruner JM, Inouye L, Fuller GN, et al. Diagnostic discrepancies and their clinical impact in a neuropathology referral practice. Cancer. 1997,79:796-803.
10. Tice H, Barnes PD, Goumnerova L, Scott RM, Tarbell NJ Pediatric and adolescent oligodendrogliomas. AJNR Am J Neuroradiol 1993, 14:1293- 1300.
11. Lee YY, Van Tassel P Intracranial oligodendrogliomas: imaging findings in 35 untreated cases. AJR Am J Roentgenol 1989,152:361-369.
12. Chin HW, Hazel JJ, Kim TH, Webster JH Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas. Cancer 1980, 45:1458-466.
13. Ironside JW, Moss TH, Louis DN, Lowe JS, Well R0 Diagnostic pathology of nervous system tumours. Churchill Livingstone, London.2002.
14. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, ed. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC), 2000.
15. Reifenberger G, Kros JM, Burger PC, et al: Oligoastrocytoma, in Kleihues P, Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Loyon, France, IARC Press, 2000, 65-69.
16. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A.Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
17. Giannini C, Scheithauer BW, Lopes MB, Hirose T, Kros JM, VandenBerg SR Immunophenotype of pleomorphic xanthoastrocytoma. Am J Surg Pathol 2002, 26:479-485.
18. Hedrum A, Ponten F, Ren Z, Lundeberg J, Ponten J, UhlenM. Sequence-based analysis of the human p53 gene based on microdissection of tumor biopsy samples. Biotechniques 1994, 17(1):118-119, 22-24, 26-29.
19. Ren ZP, Hedrum A, Ponten F, Nister M, Ahmadian A, Lundeberg J, et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 1996, 12(4):765-773.
20. Ren ZP, Sallstrom J, Sundstrom C, Nister M, Olsson Y. Recovering DNA and optimizing PCR conditions from microdissected formalin-fixed and paraffin-embedded materials. Pathobiology 2000, 68(4-5):215-217.
21. Ren ZP, Ahmadian A, Ponten F, Nister M, Berg C, LundebergJ, et al. Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin. Am J Pathol 1997, 150 (5):1791-1803.
22. Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, et al. Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques 1993, 15(1):120-127.
23. Berg C, Hedrum A, Holmberg A, Ponten F, Uhlen M, Lundeberg J. Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides. Clin Chem 1995, 41(10):1461-1466.
24. Konig EA, Koves I, Rasinariu A, Popp AR, Kusser WC, Soyonki K, et al. Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe. J Toxicol Environ Health A 2001, 62(5):333-347.
25. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
26. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
27. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002, 61(3):215-25; discussion 26-29.
28. Velasco ME, Dahl D, Roessman U, et al. Immunohistochemical localization of glial f ibrillary acidic protein in human glial neoplasms. Cancer 1980,45:484-494.
29. KleinmanGM, ZagzagD, Miller DC. Diagnostic use of immunohistochemistry in neuropathology. Neurosurg Clin N Am 1994, 5:97-126.
30. Reifenberger G, Collins VP. Pathology and molecular genetics of astrocytic gliomas. J Mol Med 2004, 82:656-670.
31. Shibata D. Pattern recognition and arrays. Am J Pathol 1999, 154:979-980.
32. Blackstock WP, Weir MP. Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 1999, 17:121-127.
33. Klein CA, Blankenstein TJ, Schmidt-Kittler O, et al. Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 2002, 360:683-689.
34. Specht K, Richter T, Muller U, et al. Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol 2001,158:419-439.
35. Fend F, Raffeld M. Laser capture microdissection in pathology. J Dlin Pathol. 2000,53:666-672.
36. Gillespie JW, Ahram M, Best CJ, et al. The role of tissue microdissection in cancer research. Cancer J 2001,7:32-39.
37. Soussi T, Asselain B, Hamroun D, Kato S, Ishioka C, Claustres M, Beroud C. Meta～analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res. 2006, 12(1): 62-9.
38. Hollstein M ,Sidransky D ,Vogelstein B , et al . p53 mutations in human cancers. Science 1991, 253(5051):49.
39. Derry WB, Putzke AP, Rothman JH, et al. Caenorhabditis elegans P53 role in apoptosis, meiosis, and stress resistance. Science 2001, 294:591-595.
40. Woo RA, Mclure KG, Lees-Miller SP, et al. DNA dependent protein kinase acts upstream of P53 in response to DNA damage. Nature 1998, 394 (6694): 700-704.
41. Ko L, Prives C. P53: puzzle and paradigm. Gene and Development 1996, 10: 1054-1072.
42. Ford JM, Hanawalt PC, et al. Role of DNA excision repair gene defects in the etiology of cancer. Current Topics Microbiology 1997, 221: 47-70.
43. Levine AJ. P53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-331.
44. Vousden KH. P53: death star. Cell 2000, 103:691-694.
45. James MC, Peters G. Alternative product of the pl6/CKDN2A locus connects the Rb and p53 tumor suppressors. Prog Cell Cycle Res 2000, 4:71-81.
46. Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 2001,264:42-55.
47. Liu MC, Gelmann EP. P53 gene mutations: case study of a clinical marker for solid tumors. Semin Oncol 2002, 29:246-257.
48. Ng HK. Pathology 1998, 30(2): 196.
49. von Deimling A, Louis DN, Wiestler OD. Molecular pathways in the formation of gliomas. Glia 1995, 15(3):328-338.
50. Kleihues P, Cavenee Wk. Pathology and genetics of tumors of the nervous system. Lyon: IARC Press 2000.
51. Ohgaki H, Kieihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005, 64(6):479-89.
52. Soussi T. The p53 tumor suppressor gene: from molecular biology to .clinical investigation. Ann N Y Acad Sci 2000, 910:121-137; discussion 137-139.
53. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
54. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
55. Bogler O, Huang HJ, Kleihues P, et al. The p53 gene and its eole in human brain tumors. Gloa 1995, 15:308-327.
56. Zupanska A, Kaminska B. The diversity of p53 mutations anong human brain tumors and their functional consequences. Neurochem Int 2002, 40:637-645.
57. Jafri A, Aziz MY, Ros S, et al. Mutations of the p53 gene in gliomas from Malay patients. Med J Malaysis 2003, 58(2):236-242.
58. van Meyel DJ, Ramsay DA, Casson AG, Keeney M, Chambers AF, Cairncross JG. p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression. J Natl Cancer Inst 1994, 86(13):1011-1017.
59. Walker C, Joyce KA, Thompson-Hehir J, Davies MP, Gibbs FE, Halliwell N, et al. Characterisation of molecular alterations in microdissected archival gliomas. Acta Neuropathol (Berl) 2001,101(4):321-333.
60. Peraud A, KrethFW, Wiestler OD, Kleihues P, Reulen HJ. Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade II astrocytomas and oligoastrocytomas. Clin Cancer Res 2002, 8(5):1117-1124.
61. Stander M, Peraud A, Leroch B, Kreth FW. Prognostic Impact of TP53 Mutation Status for Adult Patients with Supratentorial World Health Organization Grade II Astrocytoma or Oligoastrocytoma. American Cancer- Society 2004, 1028-1035.
1. Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M. Allelic Losses at 1p36 and 19q13 in Gliomas: Correlation with Histologic Classification, Definition of a 150-kb Minimal Deleted Region on 1p36, and Evaluation of CAMTA1 as a Candidate Tumor Suppressor Gene. Clin Cancer Res 2005, 11:1119-1128.
2. 赵国屏 等。生物信息学。科学出版社 2002, 75.
3. Jordan E, Collins FS. A march of genetic maps. Nature 1996, 380:111-112.
4. Mao L, Lee DJ, Tockman MS, et al. Microsatellite alterations as xlonal markers for the detection of human cancer. Proc Natl Acad Sci USA 1994, 91:9871-9875.
5. Bogdan I, Burg G, Boni R. Spitz nevi display allelic deletions. Arch Dermatol 2001, 137(11):1417-20.
6. Milanesi E, Ajmone-Marsan P, Bignotti E, et al. Molecular detection of cell line cross-contaminations using amplified fragment length polymorphism DNA fingerprinting technology. In Vitro Cell Dev Biol Anim 2003, 39(3-4): 124-30.
7. Spiekerkietter U, Eeds A, Yue Z, et al. Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations. Hum Mutat 2002, 20(6):447-51.
8. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993, 260:812-816.
9. Ionov Y, Peinado MA, Malkosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993, 363:558-561.
10. Fujimoto J, Okamoto E, Yamanaka N, et al. Flow cytometric DNA analysis of hepaticellular carcinoma. Cancer 1991, 67:939-944.
11. Gupta M, Djalilvand A, Brat DJ. Clarifying the diffuse gliomas: an update on the morphologic features and markers that discriminate oligodendroglioma from astrocytoma. Am J Clin Pathol 2005, 124(5):755-768.
12. Reifenberger J, Reifenberger G, Liu L, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994, 145:1175-1190.
13. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
14. Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
15. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473-1479.
16. Smith JS, Perry A, Borell TJ, et al. Alterations of chromosome arms lp and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18:636-645.
17. Hoang-Xuan K, He J, Huguet S, et al. Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 2001, 57:1278-1281.
18. Buckner JC, Gesme D Jr, O' Fallon JR, et al. Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol. 2003,21:251-255.
19. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004, 22:3133-3138.
20. Perry A, Fuller CE, Banerjee R, et al. Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 glioraas and oligodendroglioma mimics. Front Biosci 2003, 8:a1-a9.
21. Brat DJ, Seiferheld WF, Perry A, et al, and the Radiation Therapy Oncology Group. Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials. Neuro-oncol 2004, 6:96-103.
22. Ino Y, Zlatescu MC, Sasaki H, et al. Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome lp loss. J Neurosurg 2000, 92:983-990.
23. Schmidt MC, Antweiler S, Urban N, et al. Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 2002, 61:321-328.
24. Hill C, Hunter SB, Brat DJ. Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. Adv Anat Pathol 2003, 10:212-217.
25. von Deimling A, Eib1 RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 1992, 52(10):2987-2990.
26. Watanabe T, Nakamura M, Kros JM, et al. Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol( Berl) 2002, 103:267-275.
27. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002,61(3):215-25; discussion 26-29.
28. Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol (Berl) 2004,108(1):49-56.
29. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, et al. Shared allelic losses on chromosomes lp and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 1995, 54(1): 91-95.
30. Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK. Clonality of oligoastrocytomas. Hum Pathol 2002,33(5):528-535.
31. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nechev S, Lenartz D, et al. Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 1997, 56(10):1098-1104.
32. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, et al. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 2002,161(1):313-319.
33. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, et al. Alterations of chromosome arms lp and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18(3):636-645.
1. Surawicz TS, McCarthy BJ, Kupelian V, Jukich PJ, Bruner JM, Davis FG Descriptive epidemiology of primarybrain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990 - 1994. Neuro-oncol 1999,1:14-25.
2. Miller RW, Young JL, Novakovic B Childhood cancer. Cancer 1995, 75:395 - 405.
3. Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, Linet MS Cancer surveillance series [corrected]: brain and other central nervous system cancers:recent trends in incidence and mortality. J Natl Cancer Inst 1999, 91:1382-1390.
4. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
5. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
6. Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2nd ed. Lyon, France: IARC Press; 2000. World Health Organization Classification of Tumours.
7. Perry A. Oligodendroglial neoplasms: current concepts, misconceptions, and folklore. Adv Anat Pathol 2001,8:183-199.
8. Burger PC. What is an oligodendroglioma? Brain Pathol 2002,12:257-259.
9. Bruner JM, InouyeL, Fuller GN, et al. Diagnostic discrepancies and their clinical impact in a neuropathology referral practice. Cancer 1997, 79:796-803.
10. Tice H, Barnes PD, Goumnerova L, Scott RM, Tarbell NJ Pediatric and adolescent oligodendrogliomas. AJNR Am J Neuroradiol 1993,14:1293- 1300.
11. Lee YY, Van Tassel P Intracranial oligodendrogliomas:imaging findings in 35 untreated cases. AJR Am J Roentgenol 1989, 152:361-369.
12. Chin HW, Hazel. JJ, Kim TH, Webster JH Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas.Cancer 1980, 45:1458-466.
13. Ironside JW, Moss TH, Louis DN, Lowe JS, Well RO Diagnostic pathology of nervous system tumours. Churchill Livingstone, London 2002.
14. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, ed. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC) 2000.
15. Reif enberger G, Kros JM, Burger PC, et al: Oligoastrocytoma, in Kleihues P, Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Loyon, France, IARC Press 2000, pp65～69.
16. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
17. Giannini C, Scheithauer BW, Lopes MB, Hirose T, Kros JM, VandenBerg SR Immunophenotype of pleomorphic xanthoastrocytoma. Am J Surg Pathol 2002, 26:479-485.
18. Reifenberger G, Kaulich K, Wiestler OD, Blumcke I . Expression of the CD34 antigen in pleomorphic xanthoastrocytomas. Acta Neuropathol (Berl) 2003,105:358-364.
19. TanakaJ, HokamaY, NakamuraH Myelin basic protein as a possible marker for oligodendroglioma. Acta Pathol Jpn 1988, 38:1297-303.
20. Kashima T, Tiu SN, Merrill JE, Vinters HV, Dawson G, Campagnoni AT Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas. Cancer Res 1993, 53:170-175.
21. Monte SM de la Uniform lineage of oligodendrogliomas. Am J Pathol 1989, 135:529-540.
22. Kennedy PG, Watkins BA, Thomas DG, Noble MD Antigenic expression by cells derived from human gliomas does not correlate with morphological classification. Neuropathol Appl Neurobiol 1987, 13:327-347.
23. Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, RowitchDH, Black PM Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc Natl Acad Sci U S A 2001, 98:10851-1086.
24. Marie Y, Sanson M, Mokhtari K, Leuraud P, Kujas M, Delattre JY, Poirier J, Zalc B, Hoang-Xuan K OLIG2 as a specific marker of oligodendroglial tumour cells. Lancet 2001, 358:298-300.
25. Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y, Nagashima K Expression of the oligodendroglial lineage-associated markers Oligl and O1ig2 in different types of human gliomas. J Neuropathol Exp Neurol 2003, 62:1052-1059.
26. Kleihues P, Cavenee WK Pathology and genetics of tumours of the nervous system, 2nd edn. IARC, Lyon 2000.
27. Cavenee WK, Furnari FB, Nagane M, et al. Diffusely infiltrating astrocytomas. In: Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2~(nd) ed. Lyon, France: IARC Press; 2000:10-21. World Health Organization Classification of Tumours.
28. Hunter SB, Brat DJ, Olson JJ, et al. Alterations in molecular pathways of diffusely infiltrating glial neoplasms: application to tumor classification and anti-tumor therapy. Int J Oncol 2003, 23:857-869.
29. Hartmann C, Mueller W, von Deimling A. Pathology and molecular genetics of oligodendroglial tumors. J Mol Med. 2004,82:638-655.
30. Reifenberger G, Collins VP. Pathology and molecular genetics of astrocytic gliomas. J Mol Med. 2004, 82:656-670.
31. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473-1479.
32. Smith JS, Perry A, Borell TJ, et al. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18:636-645.
33. Kros JM, van Run PR, Alers JC, et al. Genetic aberrations in oligodendroglial tumours: an. analysis using comparative genomic hybridization (CGH). J Pathol 1999,188:282-288.
34. Smith JS, Alderete B, Minn Y, et al. Localization of common deletion regions on lp and 19q in human gliomas and their association with histological subtype. Oncogene. 1999,18:4144-4152.
35. Perry A, Fuller CE, Banerjee R, et al. Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 2003, 8:a1～a9.
36. Burger PC, Minn AY, Smith JS, et al. Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma: a study of paraffin-embedded sections. Mod Pathol 2001,14:842-853.
37. Jeuken JW, von Deimling A, Wesseling P. Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 2004,70:161-181.
38. Reifenberger J, Reifenberger G, Liu L, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994, 145:1175-1190.
39. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
40. Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
41. Hoang-Xuan K, He J, Huguet S, et al. Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 2001,57:1278-1281.
42. Buckner JC, Gesme D Jr, O' Fallon JR, et al. . Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol. 2003, 21:251-255.
43. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004, 22:3133-3138.
44. Brat DJ, Seiferheld WF, Perry A, et al, and the Radiation Therapy Oncology Group. Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials. Neuro-oncol 2004, 6:96-103.
45. Ino Y, Zlatescu MC, Sasaki H, et al. Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome lp loss. J Neurosurg 2000, 92:983-990.
46. Schmidt MC, Antweiler S, Urban N, et al. Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 2002, 61:321-328.
47. Hill C, Hunter SB, Brat DJ. Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. Adv Anat Pathol 2003, 10:212-217.
48. Hollstein M , Sidransky D , Vogelstein B , et al. p53 mutations in human cancers. Science 1991, 253(5051):49.
49. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
50. Bogler O, Huang HJ, Kleihues P, et al. The p53 gene and its eole in human brain tumors. Gloa 1995, 15:308-327.
51. Zupanska A, Kaminska B. The diversity of p53 mutations anong human brain tumors and their functional consequences. Neurochem Int 2002, 40:637-645.
52. Ng HK. Pathology 1998, 30(2):196.
53. von Deimling A, Louis DN, Wiestler 0D. Molecular pathways in the formation of gliomas. Glia 1995, 15(3):328-338.
54. Kleihues P, Cavenee Wk. Pathology and genetics of tumors of the nervous system. Lyon: IARC Press 2000.
55. Ohgaki H, Kieihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005, 64(6):479-89.
56. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
57. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
58. Ekstrand AJ, James CD, Cavenee WK, et al. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 1991, 51:2164-2172.
59. Libermann TA, Nusbaum HR, Razon N, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985, 313:144-147.
60. Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A 1992, 89:2965-2969.
61. Frederick L, Wang X Y, Eley G, et al. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000, 60:1383-1387.
62. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004, 22:133-142.
63. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001, 7:2958-2970.
64. Fuller CE, Schmidt RE, Roth KA, et al. Clinical utility of fluorescence in situ hybridization (FISH) in morphologically ambiguous gliomas with hybrid oligodendroglial/astrocytic features. J Neuropathol Exp Neurol 2003, 62:1118-1128.
65. Korshunov A, Sycheva R, Golanov A. Molecular stratification of diagnostically challenging high-grade gliomas composed of small cells: the utility of fluorescence in situ hybridization. Clin Cancer Res 2004, 10:7820-7826.
66. Perry A, Aldape KD, George DH, et al. Small cell astrocytoma: an aggressive variant that is clinicopathologically and genetically distinct from anaplastic oligodendroglioma. Cancer 2004, 101:2318-2326.
67. Burger PC, Pearl DK, Aldape K, et al. Small cell architecture; a histological equivalent of EGFR amplification in glioblastoma multiforme? J Neuropathol Exp Neurol 2001, 60:1099-1104.
68. Aldape KD, Ballman K, Furth A, et al. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J Neuropathol Exp Neurol 2004, 63:700-707.
69. Heimberger AB, Hlatky R, Suki D, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 2005, 11:1462-1466.
70. ReyJA, Bello MJ, de Campos JM, et al. Chromosomal composition of a series of 22 human low-grade gliomas. Cancer Genet Cytogenet 1987, 29:223-237.
71. Perry A, Tonk V, McIntire DD, et al. Interphase cytogenetic (in situ hybridization) analysis of astrocytomas using archival, formalin-fixed, paraffin-embedded tissue and nonfluorescent light microscopy. Am J Clin Pathol 1997, 108:166-174.
72. Wessels PH, Twijnstra A, Kessels AG, et al. Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2. Genes Chromosomes Cancer 2002, 33:279-284.
73. Hirose Y, Aldape KD, Chang S, et al. Grade II astrocytomas are subgrouped by chromosome aberrations. Cancer Genet Cytogenet 2003, 142:1-7.
74. Schrock E, Blume C, Meffert MC, et al. Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridization. Genes Chromosomes Cancer 1996, 15:199-205.
75. Kitange G, Misra A, Law M, et al. Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas. Genes Chromosomes Cancer 2005, 42:68-77.
76. Jeuken JW, Sprenger SH, Vermeer H, et al. Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about, malignant progression detected using comparative genomic hybridization. J Neurosurg 2002, 96:559-564.
77. Jeuken JW, Sprenger SH, Wesseling P, et al. Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 1999, 58:606-612.
78. Nutt CL, Mani DR, Betensky RA, et al. Gene expression - based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 2003, 63:1602-1607.
79. Nutt CL, Betensky RA, Brower MA, et al. YKL-40 is a differential diagnostic marker for histologic subtypes of highgrade gliomas. Clin Cancer Res 2005, 11:2258-2264.
1. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, cd. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC), 2000. 2000.
2. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997; 33(3): 223-38.
3. Smith JS, Jenkins RB. Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications. Front Biosci 2000; 5: D213-31.
4. Perry JR. Oligodendrogliomas: clinical and genetic correlations. Curr Opin Neurol 2001; 14(6): 705-10.
5. von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. p53 mutations are associated with 17p allelic loss in grade Ⅱ and grade Ⅲ astrocytoma. Cancer Res 1992; 52(10): 2987-90.
6. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003; 62(2): 111-26.
7. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, et al. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma, J Neuropathol Exp Neurol 1995; 54(1): 91-5.
8. Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK. Clonality of oligoastrocytomas. Hum Pathol 2002; 33(5): 528-35.
9. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nether S, Lenartz D, et al. Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 1997; 56(10): 1098-104.
10. von Deimling A, Fimmers R, Schmidt MC, Bender B, Fassbender F, Nagel J, et al. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors. J Neuropathol Exp Neurol 2000; 59(6): 544-58.
11. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994; 145(5): 1175-90.
12. Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, et al. Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 1999; 18(28): 4144-52.
13. Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol (Berl) 2004; 108(1): 49-56.
14. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, et al. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 2002; 161(1): 313-9.
15. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002; 61(3): 215-25; discussion 26-9.
16. Hedrum A, Ponten F, Ren Z, Lundeberg J, Ponten J, Uhlen M. Sequence-based analysis of the human p53 gene based on microdissection of tumor biopsy samples. Biotechniques 1994; 17(1): 118-9, 22-4, 26-9.
17. Ren ZP, Hedrum A, Ponten F, Nister M, Ahmadian A, Luudeberg J, et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 1996; 12(4): 765-73.
18. Ren ZP, Sallstrom J, Sundstrom C, Nister M, Olsson Y. Recovering DNA and optimizing PCR conditions from microdissected formalin-fixed and paraffin-embedded materials. Pathobiology 2000; 68(4-5): 215-7.
19. Ren ZP, Ahmadian A, Ponten F, Nister M, Berg C, Lundeberg J, et al. Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin. Am J Pathol 1997; 150(5): 1791-803.
20. Berg C, Hedrum A, Holmberg A, Ponten F, Uhlen M, Lundeberg J. Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides. Clin Chem 1995;41(10):1461-6.
21. Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, et al. Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques 1993;15(1):120-7.
22. Konig EA, Koves I, Rasinarin A, Popp AR, Kusser WC, Soyonki K, et al. Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe. J Toxicol Environ Health A 2001;62(5):333-47.
23. Chompret A, Brugieres L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, et al. P53 germline mutations in childhood cancers and cancer risk for carder individuals. Br J Cancer 2000;82(12):1932-7.
24. van Meyel DJ, Ramsay DA, Casson AG, Keeney M, Chambers AF, Cairncross JG. p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression.J Natl Cancer Inst 1994;86(13):1011-7.
25. Walker C, Joyce KA, Thompson-Hehir J, Davies MP, Gibbs FE, Halliwell N, et al. Charactedsation of molecular alterations in microdissected archival gliomas. Acta Neuropathol(Berl) 2001;101(4):321-33.
26. Perand A, Kreth FW, Wiestler OD, Kleihues P, Reulen HJ. Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade Ⅱ astrocytomas and oligoastrocytomas. Clin Cancer Res 2002;8(5):1117-24.
27. Hart MN, Petito CK, Earle KM. Mixed gliomas. Cancer 1974;33(1):134-40.
28. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, et al.Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000;18(3):636-45.
2. Miller RW, Young JL, Novakovic B Childhood cancer. Cancer 1995, 75:395 - 405.
3. Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, Linet MS Cancer surveillance series [corrected]: brain and other central nervous system cancers:recent trends in incidence and mortality. J Natl Cancer Inst 1999, 91:1382-1390.
4. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
5. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
6. Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2nd ed. Lyon, France: IARC Press; World Health Organization Classification of Tumours. 2000.
7. Perry A.Oligodendroglial neoplasms: current concepts, misconceptions, and folklore. Adv Anat Pathol. 2001, 8:183-199.
8. .Burger PC. What is an oligodendroglioma? Brain Pathol. 2002; 12:257-259.
9. Bruner JM, Inouye L, Fuller GN, et al. Diagnostic discrepancies and their clinical impact in a neuropathology referral practice. Cancer. 1997,79:796-803.
10. Tice H, Barnes PD, Goumnerova L, Scott RM, Tarbell NJ Pediatric and adolescent oligodendrogliomas. AJNR Am J Neuroradiol 1993, 14:1293- 1300.
11. Lee YY, Van Tassel P Intracranial oligodendrogliomas: imaging findings in 35 untreated cases. AJR Am J Roentgenol 1989,152:361-369.
12. Chin HW, Hazel JJ, Kim TH, Webster JH Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas. Cancer 1980, 45:1458-466.
13. Ironside JW, Moss TH, Louis DN, Lowe JS, Well R0 Diagnostic pathology of nervous system tumours. Churchill Livingstone, London.2002.
14. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, ed. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC), 2000.
15. Reifenberger G, Kros JM, Burger PC, et al: Oligoastrocytoma, in Kleihues P, Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Loyon, France, IARC Press, 2000, 65-69.
16. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A.Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
17. Giannini C, Scheithauer BW, Lopes MB, Hirose T, Kros JM, VandenBerg SR Immunophenotype of pleomorphic xanthoastrocytoma. Am J Surg Pathol 2002, 26:479-485.
18. Hedrum A, Ponten F, Ren Z, Lundeberg J, Ponten J, UhlenM. Sequence-based analysis of the human p53 gene based on microdissection of tumor biopsy samples. Biotechniques 1994, 17(1):118-119, 22-24, 26-29.
19. Ren ZP, Hedrum A, Ponten F, Nister M, Ahmadian A, Lundeberg J, et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 1996, 12(4):765-773.
20. Ren ZP, Sallstrom J, Sundstrom C, Nister M, Olsson Y. Recovering DNA and optimizing PCR conditions from microdissected formalin-fixed and paraffin-embedded materials. Pathobiology 2000, 68(4-5):215-217.
21. Ren ZP, Ahmadian A, Ponten F, Nister M, Berg C, LundebergJ, et al. Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin. Am J Pathol 1997, 150 (5):1791-1803.
22. Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, et al. Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques 1993, 15(1):120-127.
23. Berg C, Hedrum A, Holmberg A, Ponten F, Uhlen M, Lundeberg J. Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides. Clin Chem 1995, 41(10):1461-1466.
24. Konig EA, Koves I, Rasinariu A, Popp AR, Kusser WC, Soyonki K, et al. Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe. J Toxicol Environ Health A 2001, 62(5):333-347.
25. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
26. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
27. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002, 61(3):215-25; discussion 26-29.
28. Velasco ME, Dahl D, Roessman U, et al. Immunohistochemical localization of glial f ibrillary acidic protein in human glial neoplasms. Cancer 1980,45:484-494.
29. KleinmanGM, ZagzagD, Miller DC. Diagnostic use of immunohistochemistry in neuropathology. Neurosurg Clin N Am 1994, 5:97-126.
30. Reifenberger G, Collins VP. Pathology and molecular genetics of astrocytic gliomas. J Mol Med 2004, 82:656-670.
31. Shibata D. Pattern recognition and arrays. Am J Pathol 1999, 154:979-980.
32. Blackstock WP, Weir MP. Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 1999, 17:121-127.
33. Klein CA, Blankenstein TJ, Schmidt-Kittler O, et al. Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 2002, 360:683-689.
34. Specht K, Richter T, Muller U, et al. Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol 2001,158:419-439.
35. Fend F, Raffeld M. Laser capture microdissection in pathology. J Dlin Pathol. 2000,53:666-672.
36. Gillespie JW, Ahram M, Best CJ, et al. The role of tissue microdissection in cancer research. Cancer J 2001,7:32-39.
37. Soussi T, Asselain B, Hamroun D, Kato S, Ishioka C, Claustres M, Beroud C. Meta～analysis of the p53 mutation database for mutant p53 biological activity reveals a methodologic bias in mutation detection. Clin Cancer Res. 2006, 12(1): 62-9.
38. Hollstein M ,Sidransky D ,Vogelstein B , et al . p53 mutations in human cancers. Science 1991, 253(5051):49.
39. Derry WB, Putzke AP, Rothman JH, et al. Caenorhabditis elegans P53 role in apoptosis, meiosis, and stress resistance. Science 2001, 294:591-595.
40. Woo RA, Mclure KG, Lees-Miller SP, et al. DNA dependent protein kinase acts upstream of P53 in response to DNA damage. Nature 1998, 394 (6694): 700-704.
41. Ko L, Prives C. P53: puzzle and paradigm. Gene and Development 1996, 10: 1054-1072.
42. Ford JM, Hanawalt PC, et al. Role of DNA excision repair gene defects in the etiology of cancer. Current Topics Microbiology 1997, 221: 47-70.
43. Levine AJ. P53, the cellular gatekeeper for growth and division. Cell 1997, 88:323-331.
44. Vousden KH. P53: death star. Cell 2000, 103:691-694.
45. James MC, Peters G. Alternative product of the pl6/CKDN2A locus connects the Rb and p53 tumor suppressors. Prog Cell Cycle Res 2000, 4:71-81.
46. Rocco JW, Sidransky D. p16(MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res 2001,264:42-55.
47. Liu MC, Gelmann EP. P53 gene mutations: case study of a clinical marker for solid tumors. Semin Oncol 2002, 29:246-257.
48. Ng HK. Pathology 1998, 30(2): 196.
49. von Deimling A, Louis DN, Wiestler OD. Molecular pathways in the formation of gliomas. Glia 1995, 15(3):328-338.
50. Kleihues P, Cavenee Wk. Pathology and genetics of tumors of the nervous system. Lyon: IARC Press 2000.
51. Ohgaki H, Kieihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005, 64(6):479-89.
52. Soussi T. The p53 tumor suppressor gene: from molecular biology to .clinical investigation. Ann N Y Acad Sci 2000, 910:121-137; discussion 137-139.
53. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
54. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
55. Bogler O, Huang HJ, Kleihues P, et al. The p53 gene and its eole in human brain tumors. Gloa 1995, 15:308-327.
56. Zupanska A, Kaminska B. The diversity of p53 mutations anong human brain tumors and their functional consequences. Neurochem Int 2002, 40:637-645.
57. Jafri A, Aziz MY, Ros S, et al. Mutations of the p53 gene in gliomas from Malay patients. Med J Malaysis 2003, 58(2):236-242.
58. van Meyel DJ, Ramsay DA, Casson AG, Keeney M, Chambers AF, Cairncross JG. p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression. J Natl Cancer Inst 1994, 86(13):1011-1017.
59. Walker C, Joyce KA, Thompson-Hehir J, Davies MP, Gibbs FE, Halliwell N, et al. Characterisation of molecular alterations in microdissected archival gliomas. Acta Neuropathol (Berl) 2001,101(4):321-333.
60. Peraud A, KrethFW, Wiestler OD, Kleihues P, Reulen HJ. Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade II astrocytomas and oligoastrocytomas. Clin Cancer Res 2002, 8(5):1117-1124.
61. Stander M, Peraud A, Leroch B, Kreth FW. Prognostic Impact of TP53 Mutation Status for Adult Patients with Supratentorial World Health Organization Grade II Astrocytoma or Oligoastrocytoma. American Cancer- Society 2004, 1028-1035.
1. Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M. Allelic Losses at 1p36 and 19q13 in Gliomas: Correlation with Histologic Classification, Definition of a 150-kb Minimal Deleted Region on 1p36, and Evaluation of CAMTA1 as a Candidate Tumor Suppressor Gene. Clin Cancer Res 2005, 11:1119-1128.
2. 赵国屏 等。生物信息学。科学出版社 2002, 75.
3. Jordan E, Collins FS. A march of genetic maps. Nature 1996, 380:111-112.
4. Mao L, Lee DJ, Tockman MS, et al. Microsatellite alterations as xlonal markers for the detection of human cancer. Proc Natl Acad Sci USA 1994, 91:9871-9875.
5. Bogdan I, Burg G, Boni R. Spitz nevi display allelic deletions. Arch Dermatol 2001, 137(11):1417-20.
6. Milanesi E, Ajmone-Marsan P, Bignotti E, et al. Molecular detection of cell line cross-contaminations using amplified fragment length polymorphism DNA fingerprinting technology. In Vitro Cell Dev Biol Anim 2003, 39(3-4): 124-30.
7. Spiekerkietter U, Eeds A, Yue Z, et al. Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations. Hum Mutat 2002, 20(6):447-51.
8. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993, 260:812-816.
9. Ionov Y, Peinado MA, Malkosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993, 363:558-561.
10. Fujimoto J, Okamoto E, Yamanaka N, et al. Flow cytometric DNA analysis of hepaticellular carcinoma. Cancer 1991, 67:939-944.
11. Gupta M, Djalilvand A, Brat DJ. Clarifying the diffuse gliomas: an update on the morphologic features and markers that discriminate oligodendroglioma from astrocytoma. Am J Clin Pathol 2005, 124(5):755-768.
12. Reifenberger J, Reifenberger G, Liu L, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994, 145:1175-1190.
13. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
14. Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
15. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473-1479.
16. Smith JS, Perry A, Borell TJ, et al. Alterations of chromosome arms lp and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18:636-645.
17. Hoang-Xuan K, He J, Huguet S, et al. Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 2001, 57:1278-1281.
18. Buckner JC, Gesme D Jr, O' Fallon JR, et al. Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol. 2003,21:251-255.
19. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004, 22:3133-3138.
20. Perry A, Fuller CE, Banerjee R, et al. Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 glioraas and oligodendroglioma mimics. Front Biosci 2003, 8:a1-a9.
21. Brat DJ, Seiferheld WF, Perry A, et al, and the Radiation Therapy Oncology Group. Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials. Neuro-oncol 2004, 6:96-103.
22. Ino Y, Zlatescu MC, Sasaki H, et al. Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome lp loss. J Neurosurg 2000, 92:983-990.
23. Schmidt MC, Antweiler S, Urban N, et al. Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 2002, 61:321-328.
24. Hill C, Hunter SB, Brat DJ. Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. Adv Anat Pathol 2003, 10:212-217.
25. von Deimling A, Eib1 RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 1992, 52(10):2987-2990.
26. Watanabe T, Nakamura M, Kros JM, et al. Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol( Berl) 2002, 103:267-275.
27. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002,61(3):215-25; discussion 26-29.
28. Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol (Berl) 2004,108(1):49-56.
29. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, et al. Shared allelic losses on chromosomes lp and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J Neuropathol Exp Neurol 1995, 54(1): 91-95.
30. Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK. Clonality of oligoastrocytomas. Hum Pathol 2002,33(5):528-535.
31. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nechev S, Lenartz D, et al. Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 1997, 56(10):1098-1104.
32. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, et al. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 2002,161(1):313-319.
33. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, et al. Alterations of chromosome arms lp and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18(3):636-645.
1. Surawicz TS, McCarthy BJ, Kupelian V, Jukich PJ, Bruner JM, Davis FG Descriptive epidemiology of primarybrain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990 - 1994. Neuro-oncol 1999,1:14-25.
2. Miller RW, Young JL, Novakovic B Childhood cancer. Cancer 1995, 75:395 - 405.
3. Legler JM, Ries LA, Smith MA, Warren JL, Heineman EF, Kaplan RS, Linet MS Cancer surveillance series [corrected]: brain and other central nervous system cancers:recent trends in incidence and mortality. J Natl Cancer Inst 1999, 91:1382-1390.
4. Central Brain Tumor Registry of the United States. Statistical Report: Primary Brain Tumors in the United States, 1995-1999. Chicago, IL: Central Brain Tumor Registry of the United States; 2002.
5. Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York, NY:Churchill Livingstone; 2002.
6. Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2nd ed. Lyon, France: IARC Press; 2000. World Health Organization Classification of Tumours.
7. Perry A. Oligodendroglial neoplasms: current concepts, misconceptions, and folklore. Adv Anat Pathol 2001,8:183-199.
8. Burger PC. What is an oligodendroglioma? Brain Pathol 2002,12:257-259.
9. Bruner JM, InouyeL, Fuller GN, et al. Diagnostic discrepancies and their clinical impact in a neuropathology referral practice. Cancer 1997, 79:796-803.
10. Tice H, Barnes PD, Goumnerova L, Scott RM, Tarbell NJ Pediatric and adolescent oligodendrogliomas. AJNR Am J Neuroradiol 1993,14:1293- 1300.
11. Lee YY, Van Tassel P Intracranial oligodendrogliomas:imaging findings in 35 untreated cases. AJR Am J Roentgenol 1989, 152:361-369.
12. Chin HW, Hazel. JJ, Kim TH, Webster JH Oligodendrogliomas. I. A clinical study of cerebral oligodendrogliomas.Cancer 1980, 45:1458-466.
13. Ironside JW, Moss TH, Louis DN, Lowe JS, Well RO Diagnostic pathology of nervous system tumours. Churchill Livingstone, London 2002.
14. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, ed. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC) 2000.
15. Reif enberger G, Kros JM, Burger PC, et al: Oligoastrocytoma, in Kleihues P, Cavenee WK: Pathology and Genetics of Tumours of the Nervous System. Loyon, France, IARC Press 2000, pp65～69.
16. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
17. Giannini C, Scheithauer BW, Lopes MB, Hirose T, Kros JM, VandenBerg SR Immunophenotype of pleomorphic xanthoastrocytoma. Am J Surg Pathol 2002, 26:479-485.
18. Reifenberger G, Kaulich K, Wiestler OD, Blumcke I . Expression of the CD34 antigen in pleomorphic xanthoastrocytomas. Acta Neuropathol (Berl) 2003,105:358-364.
19. TanakaJ, HokamaY, NakamuraH Myelin basic protein as a possible marker for oligodendroglioma. Acta Pathol Jpn 1988, 38:1297-303.
20. Kashima T, Tiu SN, Merrill JE, Vinters HV, Dawson G, Campagnoni AT Expression of oligodendrocyte-associated genes in cell lines derived from human gliomas and neuroblastomas. Cancer Res 1993, 53:170-175.
21. Monte SM de la Uniform lineage of oligodendrogliomas. Am J Pathol 1989, 135:529-540.
22. Kennedy PG, Watkins BA, Thomas DG, Noble MD Antigenic expression by cells derived from human gliomas does not correlate with morphological classification. Neuropathol Appl Neurobiol 1987, 13:327-347.
23. Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, RowitchDH, Black PM Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors. Proc Natl Acad Sci U S A 2001, 98:10851-1086.
24. Marie Y, Sanson M, Mokhtari K, Leuraud P, Kujas M, Delattre JY, Poirier J, Zalc B, Hoang-Xuan K OLIG2 as a specific marker of oligodendroglial tumour cells. Lancet 2001, 358:298-300.
25. Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y, Nagashima K Expression of the oligodendroglial lineage-associated markers Oligl and O1ig2 in different types of human gliomas. J Neuropathol Exp Neurol 2003, 62:1052-1059.
26. Kleihues P, Cavenee WK Pathology and genetics of tumours of the nervous system, 2nd edn. IARC, Lyon 2000.
27. Cavenee WK, Furnari FB, Nagane M, et al. Diffusely infiltrating astrocytomas. In: Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. 2~(nd) ed. Lyon, France: IARC Press; 2000:10-21. World Health Organization Classification of Tumours.
28. Hunter SB, Brat DJ, Olson JJ, et al. Alterations in molecular pathways of diffusely infiltrating glial neoplasms: application to tumor classification and anti-tumor therapy. Int J Oncol 2003, 23:857-869.
29. Hartmann C, Mueller W, von Deimling A. Pathology and molecular genetics of oligodendroglial tumors. J Mol Med. 2004,82:638-655.
30. Reifenberger G, Collins VP. Pathology and molecular genetics of astrocytic gliomas. J Mol Med. 2004, 82:656-670.
31. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 1998, 90:1473-1479.
32. Smith JS, Perry A, Borell TJ, et al. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000, 18:636-645.
33. Kros JM, van Run PR, Alers JC, et al. Genetic aberrations in oligodendroglial tumours: an. analysis using comparative genomic hybridization (CGH). J Pathol 1999,188:282-288.
34. Smith JS, Alderete B, Minn Y, et al. Localization of common deletion regions on lp and 19q in human gliomas and their association with histological subtype. Oncogene. 1999,18:4144-4152.
35. Perry A, Fuller CE, Banerjee R, et al. Ancillary FISH analysis for 1p and 19q status: preliminary observations in 287 gliomas and oligodendroglioma mimics. Front Biosci 2003, 8:a1～a9.
36. Burger PC, Minn AY, Smith JS, et al. Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma: a study of paraffin-embedded sections. Mod Pathol 2001,14:842-853.
37. Jeuken JW, von Deimling A, Wesseling P. Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 2004,70:161-181.
38. Reifenberger J, Reifenberger G, Liu L, et al. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994, 145:1175-1190.
39. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
40. Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
41. Hoang-Xuan K, He J, Huguet S, et al. Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in tumor progression. Neurology 2001,57:1278-1281.
42. Buckner JC, Gesme D Jr, O' Fallon JR, et al. . Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. J Clin Oncol. 2003, 21:251-255.
43. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004, 22:3133-3138.
44. Brat DJ, Seiferheld WF, Perry A, et al, and the Radiation Therapy Oncology Group. Analysis of 1p, 19q, 9p, and 10q as prognostic markers for high-grade astrocytomas using fluorescence in situ hybridization on tissue microarrays from Radiation Therapy Oncology Group trials. Neuro-oncol 2004, 6:96-103.
45. Ino Y, Zlatescu MC, Sasaki H, et al. Long survival and therapeutic responses in patients with histologically disparate high-grade gliomas demonstrating chromosome lp loss. J Neurosurg 2000, 92:983-990.
46. Schmidt MC, Antweiler S, Urban N, et al. Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 2002, 61:321-328.
47. Hill C, Hunter SB, Brat DJ. Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. Adv Anat Pathol 2003, 10:212-217.
48. Hollstein M , Sidransky D , Vogelstein B , et al. p53 mutations in human cancers. Science 1991, 253(5051):49.
49. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997, 33(3):223-238.
50. Bogler O, Huang HJ, Kleihues P, et al. The p53 gene and its eole in human brain tumors. Gloa 1995, 15:308-327.
51. Zupanska A, Kaminska B. The diversity of p53 mutations anong human brain tumors and their functional consequences. Neurochem Int 2002, 40:637-645.
52. Ng HK. Pathology 1998, 30(2):196.
53. von Deimling A, Louis DN, Wiestler 0D. Molecular pathways in the formation of gliomas. Glia 1995, 15(3):328-338.
54. Kleihues P, Cavenee Wk. Pathology and genetics of tumors of the nervous system. Lyon: IARC Press 2000.
55. Ohgaki H, Kieihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005, 64(6):479-89.
56. Louis DN, Holland EC, Cairncross JG. Glioma classification. A molecular reappraisal. Am J Pathol 2001, 159:779-786.
57. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003, 62:111-126.
58. Ekstrand AJ, James CD, Cavenee WK, et al. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 1991, 51:2164-2172.
59. Libermann TA, Nusbaum HR, Razon N, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985, 313:144-147.
60. Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A 1992, 89:2965-2969.
61. Frederick L, Wang X Y, Eley G, et al. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000, 60:1383-1387.
62. Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol 2004, 22:133-142.
63. Ciardiello F, Tortora G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin Cancer Res 2001, 7:2958-2970.
64. Fuller CE, Schmidt RE, Roth KA, et al. Clinical utility of fluorescence in situ hybridization (FISH) in morphologically ambiguous gliomas with hybrid oligodendroglial/astrocytic features. J Neuropathol Exp Neurol 2003, 62:1118-1128.
65. Korshunov A, Sycheva R, Golanov A. Molecular stratification of diagnostically challenging high-grade gliomas composed of small cells: the utility of fluorescence in situ hybridization. Clin Cancer Res 2004, 10:7820-7826.
66. Perry A, Aldape KD, George DH, et al. Small cell astrocytoma: an aggressive variant that is clinicopathologically and genetically distinct from anaplastic oligodendroglioma. Cancer 2004, 101:2318-2326.
67. Burger PC, Pearl DK, Aldape K, et al. Small cell architecture; a histological equivalent of EGFR amplification in glioblastoma multiforme? J Neuropathol Exp Neurol 2001, 60:1099-1104.
68. Aldape KD, Ballman K, Furth A, et al. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J Neuropathol Exp Neurol 2004, 63:700-707.
69. Heimberger AB, Hlatky R, Suki D, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res 2005, 11:1462-1466.
70. ReyJA, Bello MJ, de Campos JM, et al. Chromosomal composition of a series of 22 human low-grade gliomas. Cancer Genet Cytogenet 1987, 29:223-237.
71. Perry A, Tonk V, McIntire DD, et al. Interphase cytogenetic (in situ hybridization) analysis of astrocytomas using archival, formalin-fixed, paraffin-embedded tissue and nonfluorescent light microscopy. Am J Clin Pathol 1997, 108:166-174.
72. Wessels PH, Twijnstra A, Kessels AG, et al. Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2. Genes Chromosomes Cancer 2002, 33:279-284.
73. Hirose Y, Aldape KD, Chang S, et al. Grade II astrocytomas are subgrouped by chromosome aberrations. Cancer Genet Cytogenet 2003, 142:1-7.
74. Schrock E, Blume C, Meffert MC, et al. Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridization. Genes Chromosomes Cancer 1996, 15:199-205.
75. Kitange G, Misra A, Law M, et al. Chromosomal imbalances detected by array comparative genomic hybridization in human oligodendrogliomas and mixed oligoastrocytomas. Genes Chromosomes Cancer 2005, 42:68-77.
76. Jeuken JW, Sprenger SH, Vermeer H, et al. Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about, malignant progression detected using comparative genomic hybridization. J Neurosurg 2002, 96:559-564.
77. Jeuken JW, Sprenger SH, Wesseling P, et al. Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 1999, 58:606-612.
78. Nutt CL, Mani DR, Betensky RA, et al. Gene expression - based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 2003, 63:1602-1607.
79. Nutt CL, Betensky RA, Brower MA, et al. YKL-40 is a differential diagnostic marker for histologic subtypes of highgrade gliomas. Clin Cancer Res 2005, 11:2258-2264.
1. Kleihues P CW. World Health Organization Classification of Tumors, Pathology & Genetics, Tumours of the Nervous System, cd. 2000. Lyon: IARC Press, International Agency for Research on Cancer (IARC), 2000. 2000.
2. Krouwer HG, van Duinen SG, Kamphorst W, van der Valk P, Algra A. Oligoastrocytomas: a clinicopathological study of 52 cases. J Neurooncol 1997; 33(3): 223-38.
3. Smith JS, Jenkins RB. Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications. Front Biosci 2000; 5: D213-31.
4. Perry JR. Oligodendrogliomas: clinical and genetic correlations. Curr Opin Neurol 2001; 14(6): 705-10.
5. von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. p53 mutations are associated with 17p allelic loss in grade Ⅱ and grade Ⅲ astrocytoma. Cancer Res 1992; 52(10): 2987-90.
6. Reifenberger G, Louis DN. Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. J Neuropathol Exp Neurol 2003; 62(2): 111-26.
7. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S, Schramm J, et al. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma, J Neuropathol Exp Neurol 1995; 54(1): 91-5.
8. Dong ZQ, Pang JC, Tong CY, Zhou LF, Ng HK. Clonality of oligoastrocytomas. Hum Pathol 2002; 33(5): 528-35.
9. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nether S, Lenartz D, et al. Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 1997; 56(10): 1098-104.
10. von Deimling A, Fimmers R, Schmidt MC, Bender B, Fassbender F, Nagel J, et al. Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors. J Neuropathol Exp Neurol 2000; 59(6): 544-58.
11. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 1994; 145(5): 1175-90.
12. Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, et al. Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 1999; 18(28): 4144-52.
13. Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol (Berl) 2004; 108(1): 49-56.
14. Mueller W, Hartmann C, Hoffmann A, Lanksch W, Kiwit J, Tonn J, et al. Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. Am J Pathol 2002; 161(1): 313-9.
15. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002; 61(3): 215-25; discussion 26-9.
16. Hedrum A, Ponten F, Ren Z, Lundeberg J, Ponten J, Uhlen M. Sequence-based analysis of the human p53 gene based on microdissection of tumor biopsy samples. Biotechniques 1994; 17(1): 118-9, 22-4, 26-9.
17. Ren ZP, Hedrum A, Ponten F, Nister M, Ahmadian A, Luudeberg J, et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 1996; 12(4): 765-73.
18. Ren ZP, Sallstrom J, Sundstrom C, Nister M, Olsson Y. Recovering DNA and optimizing PCR conditions from microdissected formalin-fixed and paraffin-embedded materials. Pathobiology 2000; 68(4-5): 215-7.
19. Ren ZP, Ahmadian A, Ponten F, Nister M, Berg C, Lundeberg J, et al. Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin. Am J Pathol 1997; 150(5): 1791-803.
20. Berg C, Hedrum A, Holmberg A, Ponten F, Uhlen M, Lundeberg J. Direct solid-phase sequence analysis of the human p53 gene by use of multiplex polymerase chain reaction and alpha-thiotriphosphate nucleotides. Clin Chem 1995;41(10):1461-6.
21. Leitner T, Halapi E, Scarlatti G, Rossi P, Albert J, Fenyo EM, et al. Analysis of heterogeneous viral populations by direct DNA sequencing. Biotechniques 1993;15(1):120-7.
22. Konig EA, Koves I, Rasinarin A, Popp AR, Kusser WC, Soyonki K, et al. Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe. J Toxicol Environ Health A 2001;62(5):333-47.
23. Chompret A, Brugieres L, Ronsin M, Gardes M, Dessarps-Freichey F, Abel A, et al. P53 germline mutations in childhood cancers and cancer risk for carder individuals. Br J Cancer 2000;82(12):1932-7.
24. van Meyel DJ, Ramsay DA, Casson AG, Keeney M, Chambers AF, Cairncross JG. p53 mutation, expression, and DNA ploidy in evolving gliomas: evidence for two pathways of progression.J Natl Cancer Inst 1994;86(13):1011-7.
25. Walker C, Joyce KA, Thompson-Hehir J, Davies MP, Gibbs FE, Halliwell N, et al. Charactedsation of molecular alterations in microdissected archival gliomas. Acta Neuropathol(Berl) 2001;101(4):321-33.
26. Perand A, Kreth FW, Wiestler OD, Kleihues P, Reulen HJ. Prognostic impact of TP53 mutations and P53 protein overexpression in supratentorial WHO grade Ⅱ astrocytomas and oligoastrocytomas. Clin Cancer Res 2002;8(5):1117-24.
27. Hart MN, Petito CK, Earle KM. Mixed gliomas. Cancer 1974;33(1):134-40.
28. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, et al.Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 2000;18(3):636-45.