腦神經上皮細胞瘤之p53基因突變的研究

中樞神經腫瘤大約占臺灣地區所有癌症的1.84%，大部份的原發性腦瘤為神經膠質細胞瘤，其中以星細胞瘤最常見，於治療後容易再發，存活率不高。最近研究顯示癌症的產生是多步驟的機制，必須累積相當的遺傳缺陷，特別是致癌基因的活化和抑癌基因的去活化。本研究以116名接受外科手術治療的腦瘤個案為研究對象，進行其腦組織中P53基因的突變分析。以聚合酶鏈鎖反應－單股構造多形性分析62個星細胞瘤、23個寡樹突細胞瘤、11個室管膜瘤、和20個原始性神經上皮細胞瘤的組織。其中的17個腦瘤組織發生p53基因突變(14.70%)，且位在表現序列5、7和8。p53突變並非隨機分佈在各類組織，而是好發於第Ⅱ、Ⅲ級星細胞瘤(17.30%)，第Ⅲ級寡樹突細胞瘤(22.2%)和原始性神經上皮細胞瘤(25%)。p53基因的突變形式皆為單一核苷酸位置的改變，大部份是誤意義的突變(85%)。G:C轉變為A:T，或C:G轉變為T:A有60%；CpG二核苷酸位置的突變率則是60%。這些結果顯示p53基因的去活化，在腦瘤發展過程中扮演極重要的角色。

關鍵字

腦神經上皮細胞瘤； p53基因

並列摘要

Tumors of the central nervous system account for approximately 1.84% of all human cancers in Taiwan. Most of adult primary brain tumors are gliomas, of which astrocytomas are the most common ones. These tumors are progressive, tend to recur following treatment, and are usually fatal. Recent studies have shown that cancers progress as a result of several sequential genetic events, occurring stepwise over time, and may involve either activation of oncogenes or inactivation of tumor suppressor genes. Tumor suppressor genes, especially p53, are now known to play an important role in the development of a wide variety of human cancers. In the study, polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis was used to investigate the mutation of p53 gene in 116 surgically removed primary brain tumor tissues which include 62 astrocytomas, 23 oligodendrogliomas, 11 ependymomas and 20 primitive neuroepithelial tumors (PNET). 14.7% (17/116) of the brain tumors had p53 mutation and were found to be localized in exons 5, 7, and 8. Mutations do not follow a random distribution among different subtypes, but occurred in 17.3% (9/52) of grade Ⅱ and Ⅲ of astrocytomas, 22.2% (2/9) of grade Ⅲ oligodendrogliomas and 25% of PNETs. All p53 mutations were single nucleotide change, mostly missense mutations (17 events). The majority of mutations identified in this study were G:C to A:T or C:G to T:A transitions (60%, 12 of 20) and occurred frequently (60%, 12 of 20) at sites of CpG dinucleotides, which are known to be hot spots for mutations in the p53 gene in many other types of human cancers. These results suggest that the inactivation of p53 gene plays an important role in the development of brain tumor.

並列關鍵字

brain tumor ； p53 gene

國際替代計量

腦神經上皮細胞瘤之p53基因突變的研究

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