Alteration of hMSH2 and DNA polymerase β genes in breast carcinomas and fibroadenomas

Genomic stability is preserved by error-free DNA replication, post-replicative proofreading, DNA repair, and recombinational events. in essence, DNA repair genes are recognized to play key roles in such stability. We report evidence for expression of the wild-type and a truncated form of DNA polymerase beta (pol beta) proteins, a base-excision repair gene, in breast carcinomas and fibroadenomas, a benign breast disease. An 87-bp deleted variant of pol beta was identified to be prevalent in microsatellite unstable breast tumors and fibroadenomas. A large deletion of 1476 bp, as well as point mutations in human MutS homolog 2 (hMSH2) cDNA, was revealed in breast carcinomas. The protein truncation assay confirmed the 1476-bp deletion as a premature protein. This is the first evidence for variant forms of hMSH2 that are associated with breast cancer. Genomic instability in the hMSH2 and pol beta genes may facilitate the occurrence of mutator phenotype in breast cancer. (C) 1999 Academic Press.