title: Alteration of hMSH2 and DNA polymerase beta genes in breast carcinomas and fibroadenomas.
abstract: 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 (polbeta) proteins, a base-excision repair gene, in breast carcinomas and fibroadenomas, a benign breast disease. An 87-bp deleted variant of polbeta 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 polbeta genes may facilitate the occurrence of mutator phenotype in breast cancer.
authors.affiliation: Department of Cancer Biology, NB40, Department of General Surgery, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bhattacharyya
authors.forename: H C
authors.initials: HC
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Grundfest-Broniatowski
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D019951:DNA Polymerase beta / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D018226:Fibroadenoma / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019951:DNA Polymerase beta; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein