title: Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue.
abstract: Evaluation of the causative role of germline mutations in DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) families can be difficult. Whereas nonsense, frameshift or splice-site mutations are presumed to lead to dysfunctional gene products and thus are generally considered to be causative, the evaluation of missense mutations often remains uncertain. We observed a novel germline mutation in the hMLH1 gene (His-->Pro at codon 329) in an HNPCC family. The same missense mutation also occurred as a somatic event in the colonic tumours of two other HNPCC patients who had germline mutations at different sites of the hMLH1 gene. Thus, the H329P mutation present in the germline can be considered as having an aetiological role in this HNPCC family.
authors.affiliation: Institute of Human Genetics, University of Bonn, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Friedl
authors.forename: C
authors.initials: C
authors.lastname: Lamberti
authors.forename: C
authors.initials: C
authors.lastname: Ruelfs
authors.forename: R
authors.initials: R
authors.lastname: Kruse
authors.forename: P
authors.initials: P
authors.lastname: Propping
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D018095:Germ-Line Mutation; D006639:Histidine; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D011392:Proline; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D006639:Histidine; D011392:Proline; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein