Mutations of two P/WS homologues in hereditary nonpolyposis colon cancer (original) (raw)

• Letter
• Published: 01 September 1994
• Nickolas Papadopoulos1,
• Bo Liu1,
• Ying-Fei Weit2,
• Kenneth C. Carter2,
• Steven M. Ruben2,
• Craig A. Rosen2,
• William A. Haseltine2,
• Robert D. Fleischmann3,
• Claire M. Fraser3,
• Mark D. Adams3,
• J. Craig Venter3,
• Malcolm G. Dunlop4,
• Stanley R. Hamilton5,
• Gloria M. Petersen6,
• Albert de la Chapelle7,
• Bert Vogelstein1 &
• …
• Kenneth W. Kinzler1,2,3

Nature volume 371, pages 75–80 (1994)Cite this article

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Abstract

HEREDITARY nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases1. Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease2–8. In particular, hMSH2 and hMLHl homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were shown to be mutated in a subset of HNPCC cases9–16. Here we report the nucleotide sequence, chromosome localization and mutational analysis of hPMSl and hPMS2, two additional homologues of the prokaryotic mutL gene. Both hPMSl and hPMS2 were found to be mutated in the germline of HNPCC patients. This doubles the number of genes implicated in HNPCC and may help explain the relatively high incidence of this disease.

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References

1. Lynch, H. T. et al. Gastroenterology 104, 1535–1549 (1993).
   Article CAS Google Scholar
2. Peinado, M. A., Malkhosyan, S., Velazquez, A. & Perucho, M. Proc. natn. Acad. Sci. U.S.A. 89, 10065–10069 (1992).
   Article ADS CAS Google Scholar
3. Ionov, Y., Peinado, A., Malkhosyan, S., Shibata, D. & Perucho, M. Nature 363, 558–561 (1993).
   Article ADS CAS Google Scholar
4. Thibodeau, S. N., Bren, G. & Schaid, D. Science 260, 816–819 (1993).
   Article ADS CAS Google Scholar
5. Aaltonen, L. A. et al. Science 260, 812–816 (1993).
   Article ADS CAS Google Scholar
6. Strand, M., Prolla, T. A., Liskay, R. M. & Petes, T. D. Nature 365, 274–276 (1993).
   Article ADS CAS Google Scholar
7. Parsons, R. P. et al. Cell 75, 1227–1236 (1993).
   Article CAS Google Scholar
8. Umar, A. et al. J. biol. chem. 269, 14367–14370 (1994).
   CAS PubMed Google Scholar
9. Peltomaki, P. et al. Science 260, 810–812 (1993).
   Article ADS CAS Google Scholar
10. Lindblom, A., Tannergard, P., Werelius, B. & Nordenskjold, M. Nature Genet. 5, 279–282 (1993).
    Article CAS Google Scholar
11. Nystrom-Lahti, M. et al. Proc. natn. Acad. Sci. U.S.A. 91, 6054–6058 (1994).
    Article ADS CAS Google Scholar
12. Fishel, R. et al. Cell 75, 1027–1038 (1993).
    Article CAS Google Scholar
13. Leach, F. S. et al. Cell 75, 1215–1225 (1993).
    Article CAS Google Scholar
14. Palombo, F., Hughes, M. & Jiricny, J. Nature 367, 417–418 (1994).
    Article ADS CAS Google Scholar
15. Bronner, C. E. et al. Nature 368, 258–261 (1994).
    Article ADS CAS Google Scholar
16. Papadopoulos, N. et al. Science 263, 1625–1629 (1994).
    Article ADS CAS Google Scholar
17. Adams, M. D. et al. Science 252, 1651–1656 (1991).
    Article ADS CAS Google Scholar
18. Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).
    Article ADS CAS Google Scholar
19. Kozak, M. Cell 44, 283–292 (1986).
    Article CAS Google Scholar
20. Prolla, T. A., Christie, D. M. & Liskay, R. M. Molec cell. Biol. 14, 407–415 (1994).
    Article CAS Google Scholar
21. Liu, B. et al. Cancer Res. (in the press).
22. Powell, S. M. et al. New Engl. J. Med. 329, 1982–1987 (1993).
    Article CAS Google Scholar
23. Van Der Luijt, R. et al. Genomics 20, 1–4 (1994). (Initials?)
    Article CAS Google Scholar
24. Dietz, H. C., et al. Science 259, 680–683 (1993).
    Article ADS CAS Google Scholar
25. Prolla, T. A. et al. Science (in the press).
26. Kramer, W., Kramer, B., Williamson, M. S. & Fogel, S. J. J. Bact. 171, 5339–5346 (1989).
    Article CAS Google Scholar
27. Schuler, G. D., Altschul, S. F. & Lipman, D. J. Proteins Struct. Funct. Genet. 9, 180–190 (1991).
    Article CAS Google Scholar
28. Johnson, C. V. et al. Meth. cell. Biol. 35, 73–99 (1991).
    Article CAS Google Scholar
29. Sidransky, D. et al. Science 252, 706–709 (1991).
    Article ADS CAS Google Scholar

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Authors and Affiliations

1. The Johns Hopkins Oncology Center, Baltimore, Maryland, 21231, USA
   Nicholas C. Nicolaides, Nickolas Papadopoulos, Bo Liu, Bert Vogelstein & Kenneth W. Kinzler
2. Human Genome Sciences, Inc., 9620 Medical Center Drive, Suite 300, Rockville, Maryland, 20850-3338, USA
   Ying-Fei Weit, Kenneth C. Carter, Steven M. Ruben, Craig A. Rosen, William A. Haseltine & Kenneth W. Kinzler
3. The Institute for Genomic Research, 932 Clopper Road, Gaithersburg, Maryland, 20878, USA
   Robert D. Fleischmann, Claire M. Fraser, Mark D. Adams, J. Craig Venter & Kenneth W. Kinzler
4. MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, UK
   Malcolm G. Dunlop
5. The Johns Hopkins University School of Medicine, Departments of Pathology and Oncology, Baltimore, Maryland, 21205, USA
   Stanley R. Hamilton
6. Department of Epidemiology, The Johns Hopkins University School of Public Health and Hygiene, Baltimore, Maryland, 21205, USA
   Gloria M. Petersen
7. Department of Medical Genetics, University of Helsinki, 00290, Helsinki, Finland
   Albert de la Chapelle

Authors

1. Nicholas C. Nicolaides
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2. Nickolas Papadopoulos
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3. Bo Liu
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4. Ying-Fei Weit
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5. Kenneth C. Carter
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6. Steven M. Ruben
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7. Craig A. Rosen
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8. William A. Haseltine
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9. Robert D. Fleischmann
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10. Claire M. Fraser
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11. Mark D. Adams
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12. J. Craig Venter
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13. Malcolm G. Dunlop
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14. Stanley R. Hamilton
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15. Gloria M. Petersen
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16. Albert de la Chapelle
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17. Bert Vogelstein
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18. Kenneth W. Kinzler
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Nicolaides, N., Papadopoulos, N., Liu, B. et al. Mutations of two P/WS homologues in hereditary nonpolyposis colon cancer.Nature 371, 75–80 (1994). https://doi.org/10.1038/371075a0

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• Received: 21 June 1994
• Accepted: 22 July 1994
• Issue Date: 01 September 1994
• DOI: https://doi.org/10.1038/371075a0