Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Cell. 1993 Dec 17;75(6):1215-25. doi: 10.1016/0092-8674(93)90330-s.


Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these patients contain alterations in microsatellite sequences (RER+ phenotype). We have used chromosome microdissection to obtain highly polymorphic markers from chromosome 2p16. These and other markers were ordered in a panel of somatic cell hybrids and used to define a 0.8 Mb interval containing the HNPCC locus. Candidate genes were then mapped, and one was found to lie within the 0.8 Mb interval. We identified this candidate by virtue of its homology to mutS mismatch repair genes. cDNA clones were obtained and the sequence used to detect germline mutations, including those producing termination codons, in HNPCC kindreds. Somatic as well as germline mutations of the gene were identified in RER+ tumor cells. This mutS homolog is therefore likely to be responsible for HNPCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism
  • Cell Line
  • Chromosome Banding
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • Colon / metabolism
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Cricetinae
  • DNA Primers
  • DNA Repair / genetics
  • DNA-Binding Proteins*
  • Fungal Proteins / genetics
  • Gene Library
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Hybrid Cells
  • In Situ Hybridization, Fluorescence
  • Mice
  • Molecular Sequence Data
  • MutS Homolog 2 Protein
  • Mutation*
  • Open Reading Frames
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Proto-Oncogene Proteins / genetics*
  • Rats
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid


  • DNA Primers
  • DNA-Binding Proteins
  • Fungal Proteins
  • Genetic Markers
  • Proto-Oncogene Proteins
  • Saccharomyces cerevisiae Proteins
  • MSH2 protein, S cerevisiae
  • MSH2 protein, human
  • Msh2 protein, mouse
  • Msh2 protein, rat
  • MutS Homolog 2 Protein

Associated data

  • GENBANK/L20821
  • GENBANK/L20822
  • GENBANK/L20823
  • GENBANK/L20888
  • GENBANK/L20889
  • GENBANK/L33709
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924
  • GENBANK/U04045