Abstract
Patients with a myelodysplastic syndrome (MDS) which has a risk of leukaemic change exhibit a variable clinical course1–3. It has been suggested that the development of leukaemia in patients with MDS may be related to chromosomal abnormalities or genetic alterations3–5: somatic mutation of the N-ras gene is now considered to be a critical step in the genetic basis of human leukaemogenesis6–14. Here we report that DNAs of bone-marrow cells from three out of eight patients with MDS contained an activated N-ras oncogene, as detected by an in vivo selection assay in nude mice with transfected NIH 3T3 cells12,15. Molecular analysis revealed the same single nucleotide substitution at codon 13 in all three transforming N-ras genes. Each of the three patients showed a progression of the disease and a resulting leukaemic change within the following year. Our observation of the mutation at codon 13 in leukaemic cell DNAs from all three cases suggests that activation of the N-ras gene is important in the development of leukaemia in some MDS cases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Coiffier, B. et al. Cancer 52, 83–90 (1983).
Mufti, G. J., Stevens, J. R., Oscier, D. G., Hamblin, T. J. & Machin, D. Br. J. Haemat. 59, 425–433 (1985).
Greenberg, P. L. Blood 61, 1035–1044 (1983).
Nowell, P. C. Cancer Genet. Cytogenet. 5, 265–278 (1982).
Clark, R. et al. New Engl. J. Med. 312, 1540–1544 (1985).
Murray, M. J. et al. Cell 33, 749–757 (1983).
Eva, A., Tronick, S. R., Gol, R. A., Pierce, J. H. & Aaronson, S. A. Proc. natn. Acad. Sci. U.S.A. 80, 4926–4930 (1983).
Souyri, M. & Fleissner, E. Proc. natn. Acad. Sci. U.S.A. 80, 6676–6679 (1983).
Bos, J. L. et al. Nucleic Acids Res. 12, 9155–9163 (1984).
Gambke, C., Signer, E. & Moroni, C. Nature 307, 476–478 (1984).
Gambke, C., Hall, A. & Moroni, C. Proc. natn. Acad. Sci. U.S.A. 82, 879–882 (1985).
Bos, J. L. et al. Nature 315, 726–730 (1985).
Hirai, H. et al. Blood 66, 1371–1378 (1985).
Needleman, S. W., Kraus, M. H., Srivastava, S. K., Levine, P. H. & Aaronson, S. A. Blood 67, 753–757 (1986).
Blair, D. G., Cooper, C. S., Oskarsson, M. K., Eader, L. A. & Vande Woude, G. M. Science 218, 1122–1124 (1982).
Bennet, J. M. et al. Br. J. Haemat. 51, 189–199 (1982).
Southern, P. J. & Berg, P. J. molec. appl. Genet. 1, 327–341 (1982).
Jelineck, W. R. et al. Proc. natn. Acad. Sci. U.S.A. 77, 1398–1402 (1980).
Taparowsky, E., Shimizu, K., Goldfarb, M. & Wigler, M. Cell 34, 581–586 (1983).
Yuasa, Y. et al. Proc. natn. Acad. Sci. U.S.A. 81, 3670–3674 (1984).
Tainsky, M. A., Cooper, C. S., Gioranella, B. C. & Vande Would, G. F. Science 225, 643–645 (1984).
Brown, R., Marshall, C. J., Pennie, S. G. & Hall, A. EMBO J. 3, 1321–1326 (1984).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hirai, H., Kobayashi, Y., Mano, H. et al. A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome. Nature 327, 430–432 (1987). https://doi.org/10.1038/327430a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/327430a0
This article is cited by
-
Multistep tumorigenesis in peripheral T cell lymphoma
International Journal of Hematology (2015)
-
Expressional changes of genes and miRNA in common megakaryocyte-erythroid progenitors from lower-risk myelodysplastic syndrome
International Journal of Hematology (2014)
-
Prevalence and clinical implications of NRAS mutations in childhood AML: a report from the Children's Oncology Group
Leukemia (2011)
-
An Update on the Biology of RAS/RAF Mutations in Colorectal Cancer
Current Colorectal Cancer Reports (2011)
-
Clinical impact of genetic and molecular markers in myelodysplastic syndromes (MDS)
memo - Magazine of European Medical Oncology (2009)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.