Microsatellite instability and mismatch repair target gene mutations in cell lines and xenografts of prostate cancer.

BACKGROUND Mismatch repair (MMR) and microsatellite instability (MSI) occur in prostate cancer, but their role has not been well documented. METHODS In 6 cell lines and 22 xenografts from prostate cancer, PCR and gel electrophoresis were performed to detect MSI by analyzing microsatellite markers BAT-25 and BAT-26 and to detect frameshift mutations in mononucleotide repeats in BAX, IGF2R, MSH3, MSH6, and TGFBR2. RESULTS Four of 6 (67%) cell lines and 3 of 22 (14%) xenografts showed MSI. At least 1 frameshift mutation was detected in the same 4 (67%) cell lines and in 5 of 22 (23%) xenografts. While MSH3 was frequently mutated in cell lines, BAX and TGFBR2 showed frequent alterations in both cell lines and xenografts. CONCLUSIONS MSI related to MMR deficiency is relatively frequent in high-grade tumors, and mutations in MSI target genes involved in cell death and proliferation appeared to be selected for during prostatic carcinogenesis. Prostate 66:660–666, 2006. © 2005 Wiley-Liss, Inc.

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