title: Spontaneous intestinal carcinomas and skin neoplasms in Msh2-deficient mice.
abstract: Hereditary nonpolyposis colorectal cancer is associated with defects in DNA mismatch repair. Here, we characterize tumor susceptibility of the recently described Msh2-deficient mouse model. Within the first year of observation, all homozygous mice succumbed to disease, with lymphomas observed in at least 80% of the cases. The majority (70%) of animals 6 months or older developed intestinal neoplasms associated with APC inactivation. Microsatellite instability was more common in carcinomas than in adenomas, but uncommon in normal tissues. Some animals (7%) developed a variety of skin neoplasms analogous to the Muir-Torre syndrome. Msh2-/- mice implicate a direct role for mismatch repair in several neoplasms with striking phenotypic similarities to humans.
authors.affiliation: Department of Medical Biophysics, Ontario Cancer Institute/Amgen Institute, University of Toronto, Ontario, Canada.
authors.forename: A H
authors.initials: AH
authors.lastname: Reitmair
authors.forename: M
authors.initials: M
authors.lastname: Redston
authors.forename: J C
authors.initials: JC
authors.lastname: Cai
authors.forename: T C
authors.initials: TC
authors.lastname: Chuang
authors.forename: M
authors.initials: M
authors.lastname: Bjerknes
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: K
authors.initials: K
authors.lastname: Hay
authors.forename: S
authors.initials: S
authors.lastname: Gallinger
authors.forename: B
authors.initials: B
authors.lastname: Bapat
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000032:analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D005656:Fungal Proteins; D007414:Intestinal Neoplasms / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D012878:Skin Neoplasms / Q000209:etiology*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051718:MutS Homolog 2 Protein