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
Lynch, H. T. et al. Gastroenterology 104, 1535–1549 (1993).
Peinado, M. A., Malkhosyan, S., Velazquez, A. & Perucho, M. Proc. natn. Acad. Sci. U.S.A. 89, 10065–10069 (1992).
Ionov, Y., Peinado, A., Malkhosyan, S., Shibata, D. & Perucho, M. Nature 363, 558–561 (1993).
Thibodeau, S. N., Bren, G. & Schaid, D. Science 260, 816–819 (1993).
Aaltonen, L. A. et al. Science 260, 812–816 (1993).
Strand, M., Prolla, T. A., Liskay, R. M. & Petes, T. D. Nature 365, 274–276 (1993).
Parsons, R. P. et al. Cell 75, 1227–1236 (1993).
Umar, A. et al. J. biol. chem. 269, 14367–14370 (1994).
Peltomaki, P. et al. Science 260, 810–812 (1993).
Lindblom, A., Tannergard, P., Werelius, B. & Nordenskjold, M. Nature Genet. 5, 279–282 (1993).
Nystrom-Lahti, M. et al. Proc. natn. Acad. Sci. U.S.A. 91, 6054–6058 (1994).
Fishel, R. et al. Cell 75, 1027–1038 (1993).
Leach, F. S. et al. Cell 75, 1215–1225 (1993).
Palombo, F., Hughes, M. & Jiricny, J. Nature 367, 417–418 (1994).
Bronner, C. E. et al. Nature 368, 258–261 (1994).
Papadopoulos, N. et al. Science 263, 1625–1629 (1994).
Adams, M. D. et al. Science 252, 1651–1656 (1991).
Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).
Kozak, M. Cell 44, 283–292 (1986).
Prolla, T. A., Christie, D. M. & Liskay, R. M. Molec cell. Biol. 14, 407–415 (1994).
Liu, B. et al. Cancer Res. (in the press).
Powell, S. M. et al. New Engl. J. Med. 329, 1982–1987 (1993).
Van Der Luijt, R. et al. Genomics 20, 1–4 (1994). (Initials?)
Dietz, H. C., et al. Science 259, 680–683 (1993).
Prolla, T. A. et al. Science (in the press).
Kramer, W., Kramer, B., Williamson, M. S. & Fogel, S. J. J. Bact. 171, 5339–5346 (1989).
Schuler, G. D., Altschul, S. F. & Lipman, D. J. Proteins Struct. Funct. Genet. 9, 180–190 (1991).
Johnson, C. V. et al. Meth. cell. Biol. 35, 73–99 (1991).
Sidransky, D. et al. Science 252, 706–709 (1991).
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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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DOI: https://doi.org/10.1038/371075a0
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