少突胶质细胞瘤的分子遗传学、病理与临床预后分析

Molecular genetic alterations,pathology and clinical prognosis in oligodendroglial tumors

目的探讨少突胶质细胞肿瘤遗传分子表型、病理和临床预后的关系。方法对51例(对)少突胶质细胞肿瘤和外周血进行DNA的提取,变性梯度凝胶电泳(DGGE)和DNA测序检测抑癌基因TP53、PTEN/MMAC1和p18突变;多重PCR检测EGFR扩增、p16/CDKN2A和p18缺失;多因素分析预后和生存期。结果26例少突胶质细胞瘤中TP53和p18突变各1例;未发现PTEN/MMAC1突变;19·2%EGFR扩增;27%p16/CDKN2A缺失。25例GBMO中TP53,p18和PTEN/MMAC1突变分别是24%、0和20%。44%EGFR扩增,48%p16/CDKN2A缺失。所有肿瘤均未见p18同源性缺失。结论缺乏TP53和PTEN/MMAC1突变是少突胶质细胞肿瘤独特的分子特性。其恶化进展和生存期短与EGFR扩增密切相关。

Purpose To investigate the correlation of the molecular profile and pathology with clinical prognosis in oligodendroglial tumors. Methods A total of 26 cases of pure oligodendrogliomas and 25 glioblastomas with an oligodendroglial component （GBMO） were analyzed in this study. The DNA was extracted from the tumor tissues and peripheral blood. Denaturing gradient gel electrophoresis （DGGE） and DNA sequencing were used to detect the mutations of TP53, PTEN/MMAC1, and p18 tumor suppressor gene. Competitive multiplex PCR was conducted to detect the homozygous deletion of the pl6/CDKN2A, p18 gene and amplification of the EGFR. Results In 25 cases of oligodendrogliomas, TP53, PTEN/MMAC1, p18 mutations, EGFR amplification, and pl6/CDKN2A homozygous deletion were observed in 1 （4%）, 0, 1 （4%） , 5（ 19. 2% ）, and 7（27% ） cases, respectively. In 25 cases of GBMO, TP53, p18 and PTEN/MMAC1 mutations were detected in 24%, 0 and 20% ; EGFR amplification in 44%, p16/CDKN2A homozygous deletions in 48% respectively, p18 was normally expressed in all of oligodendroglial tumors. Conclusions Oligodendrogliomas are characterized by rare present of TP53 and PTEN/MMAC1 mutation. The study demonstrates the unfavorable impact of EGFR amplification on the prognosis.