Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Fredrick S. Leach, Nicholas C. Nicolaides, Nickolas Papadopoulos, Bo Liu, Jin Jen, Ramon Parsons, Päivi Peltomäki, Pertti Sistonen, Lauri A. Aaltonen, Minna Nyström-Lahti, X. Y. Guan, Ji Zhang, Paul S. Meltzer, Jing Wei Yu, Fa Ten Kao, David J. Chen, Karen M. Cerosaletti, R. E.Keith Fournier, Sean Todd, Tracey LewisRobin J. Leach, Susan L. Naylor, Jean Weissenbach, Jukka Pekka Mecklin, Heikki Järvinen, Gloria M. Petersen, Stanley R. Hamilton, Jane Green, Jeremy Jass, Patrice Watson, Henry T. Lynch, Jeffrey M. Trent, Albert de la Chapelle, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

2013 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1215-1225
Number of pages11
Issue number6
StatePublished - Dec 17 1993

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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