Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Mutations of two P/WS homologues in hereditary nonpolyposis colon cancer

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

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

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 

Download references

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nickolas Papadopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying-Fei Weit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenneth C. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steven M. Ruben
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Craig A. Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. William A. Haseltine
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robert D. Fleischmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Claire M. Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mark D. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J. Craig Venter
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Malcolm G. Dunlop
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Stanley R. Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Gloria M. Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Albert de la Chapelle
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Bert Vogelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Kenneth W. Kinzler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/371075a0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing