title: Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-polyposis colorectal cancer families.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC), the most common hereditary colon cancer syndrome, is a dominant disorder caused by germline defects in mismatch repair (MMR) genes. Identification of MMR gene mutations can have direct clinical implications in counseling and management of HNPCC families. We screened 44 HNPCC and 97 suspected HNPCC Korean families for germline mutations in three MMR genes: MLH1, MSH2 and MSH6. We identified twelve novel mutations: nine in MLH1(c.632_633insT, c.808_811delACTT, c.845C>G, c.1625A>C, c.1730+1delG, c.1907T>C, c.1918C>T, c.2104-2A>G and c.2170T>A), two in MSH2 (c.1886A>G, c.1316_1318delCCT) and one in MSH6 (c.3488A>T). In addition, two statically significant cSNPs in MLH1: c.1128T>C ( p=0.008 in HNPCC and p=0.037 in early-onset CRC) and c.2168C>A ( p<0.001 in HNPCC). Interestingly, the most frequent mutation, c.1757_1758insC in MLH1, was a founder mutation inherited from a common Korean ancestor.
authors.affiliation: Korean Hereditary Tumor Registry, Cancer Research Institute and Cancer Research Center, Seoul National University, Seoul, 110-744, Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Shin
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Shin
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Hong
authors.forename: Ja-Lok
authors.initials: JL
authors.lastname: Ku
authors.forename: Byong-Chul
authors.initials: BC
authors.lastname: Yoo
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Jae-Gahb
authors.initials: JG
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D005787:Gene Frequency; D005838:Genotype; D018095:Germ-Line Mutation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein