title: Mutational analysis of the hMSH6 gene in familial and early-onset colorectal and endometrial cancer in Israeli patients.
abstract: Familial colorectal cancer (CRC) is noted in about 15% of incident CRC cases, and at times is hallmarked by an age at diagnosis less than 50 years. Familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC) account for about 40% of familial cases. Thus, the majority of familial and early-onset CRC remain genetically elusive. Similarly, the majority of familial and early onset endometrial cancer (EC), the most prevalent extracolonic tumor in HNPCC, are genetically undefined. An attractive candidate is the hMSH6 gene. Israeli patients with early onset (age under 50 years) (n = 44) and familial nonsyndromic (n = 23) CRC, and women with familial clustering of EC or CRC (n = 12), and those diagnosed with EC at, or under, the age of 50 years (n = 5) were genotyped for germ-line mutations within the hMSH6 gene. Exon-specific PCR was followed by denaturing gradient gel electrophoresis (DGGE) analysis, complemented by DNA sequencing of abnormally migrating fragments. No patients displayed a truncating mutation, and 1 CRC patient harbored a novel missense mutation (V878A). In addition, 6 previously described polymorphisms were detected. In conclusion, mutations in the hMSH6 gene occur uncommonly in Israeli patients with familial and early-onset CRC and EC.
authors.affiliation: Oncology Institute, the Elias Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Figer
authors.forename: Anna
authors.initials: A
authors.lastname: Kaplan
authors.forename: Ravit
authors.initials: R
authors.lastname: Geva
authors.forename: Dov
authors.initials: D
authors.lastname: Flex
authors.forename: Michal
authors.initials: M
authors.lastname: Yaron
authors.forename: Tali
authors.initials: T
authors.lastname: Levy
authors.forename: Einat Even
authors.initials: EE
authors.lastname: Sapir
authors.forename: Herma H
authors.initials: HH
authors.lastname: Fidder
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel; D008297:Male; D008875:Middle Aged
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein