title: Phenotypic analysis of hMSH2 mutations in mouse cells carrying human chromosomes.
abstract: Conversion of diploidy to haploidy is a method that allows the generation of stable murine/human hybrid cell lines carrying selected human chromosomes in only a single copy. In this setting, it is possible to detect genetic mutations with greater sensitivity and reliability than in diploid cells. Using this method, we were able to identify mutations in the human mismatch repair (MMR) gene hMSH2 in hereditary nonpolyposis colon cancer families, which have escaped detection by the conventional methods. In this report, we show that such hybrid cell lines can also be a valuable tool in the study of the mutated MMR proteins, in particular the variants found in hereditary nonpolyposis colon cancer families that carry missense mutations and where it is unclear whether they predispose to colon cancer. This analysis is made possible by the fact that the human hMSH2 protein is able to complement the MMR defect in the host murine cell line.
authors.affiliation: Institute of Medical Radiobiology, University of Zürich and Paul Scherrer Institute, CH-8008 Zürich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Marra
authors.forename: S
authors.initials: S
authors.lastname: D'Atri
authors.forename: H
authors.initials: H
authors.lastname: Yan
authors.forename: C
authors.initials: C
authors.lastname: Perrera
authors.forename: E
authors.initials: E
authors.lastname: Cannavo'
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: J
authors.initials: J
authors.lastname: Jiricny
mesh_terms: D000483:Alleles; D000818:Animals; D020137:Base Pair Mismatch; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D051718:MutS Homolog 2 Protein; D009154:Mutation; D020125:Mutation, Missense; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C102997:Msh6 protein, mouse; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein