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Korean Journal of Obstetrics & Gynecology 2005;48(5):1229-1240.
Published online May 1, 2005.
Identification of Target Genes in the Endometrial Carcinomas with Microsatellite Mutator Phenotype.
Kwon Tae You, Hoguen Kim, Tchan Kyu Park, In Sook Sohn, Ji Young Lee, Dong Wook Jang, Won Gyu Yang, Soo Nyung Kim
1Department of Obstetrics and Gynecology, College of Medicine, Konkuk University, Seoul, Korea. snkim@kku.ac.kr
2Department of Pathology, College of Medicine, Yonsei University, Seoul, Korea.
3Department of Obstetrics and Gynecology, College of Medicine, Yonsei University, Seoul, Korea.
Abstract
OBJECTIVE
Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability (MSI), exist in the endometrial carcinomas. Tumors with microsatellite mutator phenotype (MMP) are caused by defects in DNA mismatch repair genes. MMP tumors are believed to progress by accumulating frameshift mutations in coding microsatellite sequences of various cancer related genes including tumor suppressor genes, apoptosis related genes and DNA repair genes. Thus, the identification of the specific target genes in the MMP endometrial carcinomas is important for the elucidation of molecular pathogenesis of endometrial carcinomas. METHODS: We classified the MMP endometrial carcinomas and evaluated the frameshift mutations of the 11 genes containing coding microsatellite sequences by using 34 endometrial carcinomas and 4 MMP endometrial carcinoma cell lines. RESULTS: MSI was found in 6 of 34 endometrial carcinomas. In the endometrial carcinoma tissues, frequent mutations were found in TAF1B (68%), HT001 (50%), SLC23A1 (50%) and ACVR II (50%) in the MMP endometrial carcinoma tissues. The other 7 genes were infrequently mutated. Mutations of these target genes were more frequent in MMP endometrial carcinoma cell lines. CONCLUSION: we identified specific target genes in MMP endometrial carcinomas. These data demonstrate the mechanism of tumor progression in the MMP endometrial carcinomas.
Key Words: DNA mismatch repair, Microsatellite mutator phenotype, Target gene, Frameshift mutation, Endometrial carcinoma


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