title: Putative common origin of two MLH1 mutations in Italian-Quebec hereditary non-polyposis colorectal cancer families.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common inherited cancer syndromes, accounting for 3-5% of all cases of colorectal cancer. In most HNPCC families, the disease is caused by a germline mutation in MLH1 or MSH2. In some populations, founder mutations appear to explain a substantial fraction of HNPCC. We report here the identification and preliminary characterization of two putative MLH1 founder mutations. The mutation MLH1c.1831delAT was shown to segregate in two Quebec families of Italian origin who fulfilled the Amsterdam criteria for HNPCC. Haplotype analysis using five intragenic microsatellite/single nucleotide polymorphism markers spanning MLH1 on chromosome 3 showed that these two unrelated families share an identical haplotype. In addition, two other Italian kindred whose affected members carry MLH1g.IVS6 + 3A>G also share a common haplotype, suggesting that, similarly, the latter mutation has a common origin. These mutations are the first putative founder MLH1 mutations to be identified in HNPCC kindred of Italian origin.
authors.affiliation: Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Thiffault
authors.forename: W D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: V A
authors.initials: VA
authors.lastname: Marcus
authors.forename: D
authors.initials: D
authors.lastname: Farber
authors.forename: L
authors.initials: L
authors.lastname: Kasprzak
authors.forename: E
authors.initials: E
authors.lastname: MacNamara
authors.forename: N
authors.initials: N
authors.lastname: Wong
authors.forename: P
authors.initials: P
authors.lastname: Hutter
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: L
authors.initials: L
authors.lastname: Bertario
authors.forename: G
authors.initials: G
authors.lastname: Chong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D019143:Evolution, Molecular; D018703:Founder Effect; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy / Q000208:ethnology; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D011792:Quebec; D017422:Sequence Analysis, DNA
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1