MOLECULAR GENETICS OF HUMAN GYNECOLOGIC PATHOLOGY

女性生殖道肿瘤包括子宫内膜癌、子宫肉瘤、子宫平滑肌瘤和卵巢癌的分子遗传学分析正在研究中。在确定这些肿瘤的分子遗传基础方面取得了重大进展，包括通常维持基因组稳定性的途径中的缺陷。对这些癌症，特别是子宫内膜癌的分析已经定义了一个具有微卫星不稳定分子遗传表型的亚群。微卫星不稳定是DNA错配修复缺陷的结果，而DNA错配修复通常起着纠正DNA复制错误的作用。该途径的失活可能涉及几个基因的突变或表观遗传沉默。目前的研究涉及表观遗传失活的机制以及该途径在癌变中的作用。我们目前正在确定不稳定的基因靶标，这可能与人类肿瘤的发展有关。此外，我们正在研究错配修复蛋白在细胞氧化应激反应和线粒体损伤修复中的作用。今年将是这个项目的最后一年。这些项目的一个子集将在项目ES- 23003中进行。子宫内膜、错配修复、单链构象多态性检测（SSCP）、癌症、PTEN

The molecular genetics analysis of neoplastic conditions of the female genital tract including endometrial carcinoma, uterine sarcoma, uterine leiomyoma and ovarian carcinoma are under study. Significant progress has been achieved in defining the molecular genetic basis of these tumors including defects in pathways that normally function to maintain the stability of the genome. Analysis of these cancers, particularly endometrial cancer has defined a subset that has the molecular genetic phenotype of microsatellite instability. Microsatellite instability is the result of defective DNA mismatch repair, which normally functions to correct DNA replication errors. Inactivation of this pathway may involve mutation or epigenetic silencing of several genes. Current study involves the mechanism for the epigenetic inactivation as well as the contribution of this pathway to carcinogenesis. We are currently defining the genetic targets of instability that may be implicated in human tumor development. In addition, we are studying the role of mismatch repair proteins in the cellular response to oxidant stress and repair of mitochondrial damage. This will be the final year for this project. A subset of these projects will be conducted in project ES- 23003 beginning FY00. - endometrium, mismatch repair, single stranded conformation polymorphism detection (SSCP), cancer, PTEN