Microsatellite instability and frameshift mutations in genes involved in cell cycle progression or apoptosis in ovarian cancer

The loss of mismatch repair enzymes increases the mutation rate in microsat ellites and coding regions of the genome and appears to be involved in drug resistance. The replication error (RER+) phenotype, associated with micros atellite instability, has been widely described for both familial and spora dic colon cancers and for gastric and endometrial tumors. For ovarian cance r, the incidence of RER+ cases among sporadic tumors is still uncertain. We analyzed epithelial ovarian tumors and ovarian carcinoma cell lines for mi crosatellite instability and for mutations in the coding regions of differe nt genes, including the recently discovered human CHK-1 gene, which has an important role in controlling cell cycle progression and whose coding regio n contains a poly(A), tract. Microsatellite instability and frameshift muta tions in coding regions of BAX, TGF beta RII, IGFIIR, E2F-4, ICE, and CHK-1 genes were analyzed in ovarian cancer samples and cell lines by polymerase chain reaction (PCR). Approximately 26% of patients showed microsatellite instability in two or more loci. BAT-26 locus showed no alteration in prima ry tumors. We detected a BAX mutation in one tumor sample and a TGF beta RI I mutation in one cell line. Our Findings confirm the presence of the RERphenotype in sporadic ovarian cancer. The low rate of mutation in genes pre viously reported to be altered in colon and gastric cancer suggests that ot her not yet identified genes might he altered and could play a role in tumo r progression and response to treatment in RER+ ovarian turners.