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A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome

Nature volume 327, pages 430–432 (1987)Cite this article

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.

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Authors and Affiliations

  1. The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Tokyo, 113, Japan

    Hisamaru Hirai, Yukio Kobayashi, Hiroyuki Mano, Koichi Hagiwara, Yoshiro Maru, Junji Nishida & Fumimaro Takaku

  2. The Third Department of Internal Medicine, Gumma University School of Medicine, Maebashi, Gumma, 371, Japan

    Mitsuhiro Omine

  3. The Division of Hematology, Department of Medicine, Tokyo Women's Medical College, Shinjuku-ku, Tokyo, 162, Japan

    Hideaki Mizoguchi

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  1. Hisamaru Hirai
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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

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