title: Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer and linked to germline defects in at least four mismatch repair genes. Although much has been learned about the molecular pathogenesis of this disease, questions related to effective presymptomatic diagnosis are largely unanswered because of its genetic complexity. In this study, we evaluated tumors from 74 HNPCC kindreds for genomic instability characteristic of a mismatch repair deficiency and found such instability in 92% of the kindreds. The entire coding regions of the five known human mismatch repair genes were evaluated in 48 kindreds with instability, and mutations were identified in 70%. This study demonstrates that a combination of techniques can be used to genetically diagnose tumor susceptibility in the majority of HNPCC kindreds and lays the foundation for genetic testing of this relatively common disease.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: N C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: P
authors.initials: P
authors.lastname: Watson
authors.forename: J R
authors.initials: JR
authors.lastname: Jass
authors.forename: M
authors.initials: M
authors.lastname: Dunlop
authors.forename: A
authors.initials: A
authors.lastname: Wyllie
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: A
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins; D005190:Family; D005799:Genes, Dominant; D052138:Genes, Neoplasm; D006801:Humans; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D011506:Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D011506:Proteins; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1