Alteration of hMSH2 and DNA polymerase beta genes in breast carcinomas andfibroadenomas

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