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

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES023001-10
Application #
6289922
Study Section
Special Emphasis Panel (LMC)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Zhou, Y; Kato, H; Shan, D et al. (1999) Involvement of mutations in the DPC4 promoter in endometrial carcinoma development. Mol Carcinog 25:64-72