title: Mismatch repair deficiency in phenotypically normal human cells.
abstract: Tumor cells in patients with hereditary nonpolyposis colorectal cancer (HNPCC) are characterized by a genetic hypermutability caused by defects in DNA mismatch repair. A subset of HNPCC patients was found to have widespread mutations not only in their tumors, but also in their non-neoplastic cells. Although these patients had numerous mutations in all tissues examined, they had very few tumors. The hypermutability was associated with a profound defect in mismatch repair at the biochemical level. These results have implications for the relation between mutagenesis and carcinogenesis, and they suggest that mismatch repair deficiency is compatible with normal human development.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: G M
authors.initials: GM
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Longley
authors.forename: P
authors.initials: P
authors.lastname: Modrich
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Berk
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D001483:Base Sequence; D002461:Cell Line, Transformed; D002999:Clone Cells; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004276:DNA, Satellite / Q000032:analysis; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008214:Lymphocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004276:DNA, Satellite