TY - JOUR
T1 - Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer
AU - Leach, Fredrick S.
AU - Nicolaides, Nicholas C.
AU - Papadopoulos, Nickolas
AU - Liu, Bo
AU - Jen, Jin
AU - Parsons, Ramon
AU - Peltomäki, Päivi
AU - Sistonen, Pertti
AU - Aaltonen, Lauri A.
AU - Nyström-Lahti, Minna
AU - Guan, X. Y.
AU - Zhang, Ji
AU - Meltzer, Paul S.
AU - Yu, Jing Wei
AU - Kao, Fa Ten
AU - Chen, David J.
AU - Cerosaletti, Karen M.
AU - Fournier, R. E.Keith
AU - Todd, Sean
AU - Lewis, Tracey
AU - Leach, Robin J.
AU - Naylor, Susan L.
AU - Weissenbach, Jean
AU - Mecklin, Jukka Pekka
AU - Järvinen, Heikki
AU - Petersen, Gloria M.
AU - Hamilton, Stanley R.
AU - Green, Jane
AU - Jass, Jeremy
AU - Watson, Patrice
AU - Lynch, Henry T.
AU - Trent, Jeffrey M.
AU - de la Chapelle, Albert
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
N1 - Funding Information:
The authors thank S. Booker, S. M. Stewart, J. Cavalieri, S. Slominski, and S. Luscombe for clinical coordination and specimen collection; J. M. Jessup for providing tumor cell lines and xenografts; P. Gold and M. Cunningham for assistance and advice with Pl cloning; M. Castro for oligonucleotide synthesis; J. A. Pietenpol, L.-K. Su, and T. Tokino for critically reading the manuscript; and T. Gwiazda for preparing it. Thisworkwassupported bytheclayton Fund, the Folkhll-san Institute of Genetics, the Academy of Finland, the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Health Research Council and Cancer Society of New Zealand, the Auckland Medical Research Foundation, Nebraska State Health Department of Cancer, the Council for Tobacco Research, American Cancer Society, Depart-mentof Energy grants DOEIERNIFl39and DE-FG0291 ER-61139, and grants CA35494. CA09320, CA47527, GM26449, CA09243, CA41 163, CA57435, and CA42705 from the National Institutes of Health. B. V. is an American Cancer Society Research Professor.
PY - 1993/12/17
Y1 - 1993/12/17
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0027145633
UR - https://www.scopus.com/pages/publications/0027145633#tab=citedBy
U2 - 10.1016/0092-8674(93)90330-S
DO - 10.1016/0092-8674(93)90330-S
M3 - Article
C2 - 8261515
AN - SCOPUS:0027145633
SN - 0092-8674
VL - 75
SP - 1215
EP - 1225
JO - Cell
JF - Cell
IS - 6
ER -