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 Lewis & 15 others Robin 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

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Abstract

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
Pages (from-to)1215-1225
Number of pages11
JournalCell
Volume75
Issue number6
DOIs
StatePublished - Dec 17 1993

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Hereditary Nonpolyposis Colorectal Neoplasms
Chromosomes
Genes
Mutation
Germ-Line Mutation
Tumors
Microdissection
Microsatellite Repeats
DNA Mismatch Repair
Terminator Codon
Hybrid Cells
Repair
Complementary DNA
Genetic Markers
Cells
Neoplasms
Clone Cells
Phenotype

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Molecular Biology

Cite this

Leach, F. S., Nicolaides, N. C., Papadopoulos, N., Liu, B., Jen, J., Parsons, R., ... Vogelstein, B. (1993). Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell, 75(6), 1215-1225. https://doi.org/10.1016/0092-8674(93)90330-S

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

In: Cell, Vol. 75, No. 6, 17.12.1993, p. 1215-1225.

Research output: Contribution to journalArticle

Leach, FS, Nicolaides, NC, Papadopoulos, N, Liu, B, Jen, J, Parsons, R, Peltomäki, P, Sistonen, P, Aaltonen, LA, Nyström-Lahti, M, Guan, XY, Zhang, J, Meltzer, PS, Yu, JW, Kao, FT, Chen, DJ, Cerosaletti, KM, Fournier, REK, Todd, S, Lewis, T, Leach, RJ, Naylor, SL, Weissenbach, J, Mecklin, JP, Järvinen, H, Petersen, GM, Hamilton, SR, Green, J, Jass, J, Watson, P, Lynch, HT, Trent, JM, de la Chapelle, A, Kinzler, KW & Vogelstein, B 1993, 'Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer', Cell, vol. 75, no. 6, pp. 1215-1225. https://doi.org/10.1016/0092-8674(93)90330-S
Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215-1225. https://doi.org/10.1016/0092-8674(93)90330-S
Leach, Fredrick S. ; Nicolaides, Nicholas C. ; Papadopoulos, Nickolas ; Liu, Bo ; Jen, Jin ; Parsons, Ramon ; Peltomäki, Päivi ; Sistonen, Pertti ; Aaltonen, Lauri A. ; Nyström-Lahti, Minna ; Guan, X. Y. ; Zhang, Ji ; Meltzer, Paul S. ; Yu, Jing Wei ; Kao, Fa Ten ; Chen, David J. ; Cerosaletti, Karen M. ; Fournier, R. E Keith ; Todd, Sean ; Lewis, Tracey ; Leach, Robin J. ; Naylor, Susan L. ; Weissenbach, Jean ; Mecklin, Jukka Pekka ; Järvinen, Heikki ; Petersen, Gloria M. ; Hamilton, Stanley R. ; Green, Jane ; Jass, Jeremy ; Watson, Patrice ; Lynch, Henry T. ; Trent, Jeffrey M. ; de la Chapelle, Albert ; Kinzler, Kenneth W. ; Vogelstein, Bert. / Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. In: Cell. 1993 ; Vol. 75, No. 6. pp. 1215-1225.
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abstract = "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.",
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AU - Parsons, Ramon

AU - Peltomäki, Päivi

AU - Sistonen, Pertti

AU - Aaltonen, Lauri A.

AU - Nyström-Lahti, Minna

AU - Guan, X. Y.

AU - Zhang, Ji

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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

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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.

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