脑胶质瘤中EGFR基因扩增和10号染色体杂合性丢失的研究

Amplification of EGFR Gene and Loss of Heterozygosity on Chromosome 10 in Human Gliomas

目的:探索表皮生长因子受体(EGFR)基因扩增及10号染色体杂合性丢失(LOH10)与胶质瘤发生、发展的关系。方法:采用Southern印迹杂交和RFLP方法对55例各种类型的脑胶质瘤的EGFR基因扩增和10号染色体杂合性丢失情况进行检测分析。结果:17例Ⅲ—Ⅳ级恶性星型细胞肿瘤中的7例(7/17),1例髓母细胞瘤(1/10),1例极性成胶质细胞瘤(1/5)和1例室管膜母细胞瘤,存在EGFR基因的扩增和/或重排。6例Ⅲ—Ⅳ级高恶性星型细胞肿瘤(6/17)和1例髓母细胞瘤(1/10)存在10号染色体的丢失。15例Ⅰ—Ⅱ级星型细胞肿瘤和7例室管膜瘤中未见EGFR扩增和10号染色体丢失。结论:EGFR基因扩增和10号染色体丢失在各种级别的胶质瘤中的分布是非随机的,这两种遗传改变的概率随着恶性程度的增加而增大,提示EGFR基因扩增(或重排)和10号染色体的丢失与恶性胶质瘤的发展相关。

Objective: To identify the EGFR gene and the loss of heterozygosity on chromosome 10 in human gliomas. Methods: Amplification of the epidermal growth factor receptor (EGFP) and loss of huterozygosity (LOH) at loci on chromosome 10 in 55 gliomas of different grades of malignancy were determined respectively, using Southern blot method and RFLP analysis. Results: EGFR gene amplification was found in 7 of 17(41%) more malignant astrocytomas (WHO Ⅲ -Ⅳ) , 1 of 10 medulloblastomas, 1 of 5 spongioblastoma, and 1 of hypendymoglioblast. Loss of heterozygosity at loci on chromosome 10 was observed in 6 of 17(35%) more malignant astrocytomas, 1 of 10 medulloblastomas. Neither the EGFR gene amplification nor the loss of heterozygosity on chro-mosome 10 occurred in 15 low - grade (WHO I - Ⅱ ) astrocytomas and 7 eppendymomas. Conclusion: The two genetic aberrations did not fallow a random distribution in different malignancy grades. The frequencies of the EGFR gene amplification and the loss of heterozygosity on chromosome 10 signficantly increased with the malignancy grade. This analysis suggests that the EGFR gene ampli-fication and the loss of heterozygosity on chromosome 10 may play roles in the progression of gliomas.