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; 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

doi:10.1016/0092-8674(93)90330-S

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

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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 language	English
Pages (from-to)	1215-1225
Number of pages	11
Journal	Cell
Volume	75
Issue number	6
DOIs	https://doi.org/10.1016/0092-8674(93)90330-S
State	Published - 17 Dec 1993
Externally published	Yes

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Leach, F. S., Nicolaides, N. C., Papadopoulos, N., Liu, B., Jen, J., Parsons, R., Peltomäki, P., Sistonen, P., Aaltonen, L. A., Nyström-Lahti, M., Guan, X. Y., Zhang, J., Meltzer, P. S., Yu, J. W., Kao, F. T., Chen, D. J., Cerosaletti, K. M., Fournier, R. E. K., Todd, S., ... 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

@article{cd7d51f8990d4bf691a8d9822ade2341,

title = "Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer",

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.",

author = "Leach, {Fredrick S.} and Nicolaides, {Nicholas C.} and Nickolas Papadopoulos and Bo Liu and Jin Jen and Ramon Parsons and P{\"a}ivi Peltom{\"a}ki and Pertti Sistonen and Aaltonen, {Lauri A.} and Minna Nystr{\"o}m-Lahti and Guan, {X. Y.} and Ji Zhang and Meltzer, {Paul S.} and Yu, {Jing Wei} and Kao, {Fa Ten} and Chen, {David J.} and Cerosaletti, {Karen M.} and Fournier, {R. E.Keith} and Sean Todd and Tracey Lewis and Leach, {Robin J.} and Naylor, {Susan L.} and Jean Weissenbach and Mecklin, {Jukka Pekka} and Heikki J{\"a}rvinen and Petersen, {Gloria M.} and Hamilton, {Stanley R.} and Jane Green and Jeremy Jass and Patrice Watson and Lynch, {Henry T.} and Trent, {Jeffrey M.} and {de la Chapelle}, Albert and Kinzler, {Kenneth W.} and Bert Vogelstein",

note = "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.",

year = "1993",

month = dec,

day = "17",

doi = "10.1016/0092-8674(93)90330-S",

language = "English",

volume = "75",

pages = "1215--1225",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

}

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

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 - http://www.scopus.com/inward/record.url?scp=0027145633&partnerID=8YFLogxK

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 -

Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer

Abstract

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