食管癌组织的遗传不稳定性研究

Genetic Instability in Esophageal Carcinoma

目的:探讨食管癌组织遗传多态性及基因组甲基化改变在其发生或发展中的作用。方法:1)用PCR-AFLP和基因扫描的方法,对食管癌组织与癌旁组织AR基因、Rb基因(intron16、17)、ER基因(PvuII和XbaI)和cbl2基因6个多态位点的检测。2)用HPLC的方法,对食管癌组织与癌旁组织基因组DNA甲基化的水平检测。结果:35例患者中至少一个位点发生改变者占74.29%,在不同级别的食管癌组织中多态性改变各为:Ⅰ:9/12(75%);Ⅱ:13/15(85%);Ⅲ:4/8(50%)。在食管癌早期癌组织基因组甲基化水平比癌旁组织低,随着肿瘤的进程甲基化水平逐渐上升,甚至超过了癌旁组织。结论:从食管癌组织早期基因组低甲基化与大量的多态性改变,推测遗传不稳定性是食管癌发生发展中普遍事件,早期基因组甲基化的降低可能与其遗传不稳定性的产生关系密切。

Objective： To investigate the effects of genetic polymorphisms and alterations in methylation patterns on oncogenesis and progression of esophageal cancer. Methods： a） Six polymorphic sites （AR, Rb17, Rb16, ER-pvuⅡ, ER-XbaI and cbl2） from the cancerous and paraneoplastic tissues from 35 patients with esophageal squamous cell cancer （ESCC） were analyzed using polymerase chain reaction-amplified fragment length polymorphism （PCR-AFLP） and Genescan software. b） The genomic methylation level in the cancerous and paraneoplastic tissues was assayed using HPLC. Results： Alteration of at least one site occurred in 26 of the 35 patients （74.3%）. The changes at the polymorphic site in different stages were as follows： 9/12 （75%） in stage Ⅰ, 13/15 （85%） in stage Ⅱ, and 4/8 （50%） in stage Ⅲ. The total genomic DNA methylation level in early esophageal cancer was lower than that of the paraneoplastic tissues, but it surpassed the paraneoplastic tissues as the methylation level gradually increased with the process of tumor cell differentiation. Conclusions： It is presumed that genetic instability is a common event in the genesis and development of esophageal carcinoma. Genomic instability in esophageal carcinoma may be related to the decreased genomic methylation in patients with early esophageal cancer.