Ras Mutations in Primary Myelodysplasia and in Patients Following Cytotoxic Therapy

  • A. Jacobs
  • R. A. Padua
  • G. Carter
  • D. Hughes
  • R. E. Clark
  • D. Oscier
  • D. Bowen
  • J. F. McCormick

Abstract

The ras gene family, H-ras, K-ras and N-ras, code for 21kD proteins that have GTPase activity and have been implicated in the control of cell proliferation (McKay et al. 1986; Trahey et al. 1987). Mutations in these genes give rise to abnormal protein products that have the capacity to transform certain cells to a malignant phenotype. Ras mutations have been found in a wide range of human malignancies and N-ras has been particularly implicated in AML, chronic myeloid leukaemia (CML), and acute lymphoblastic leukaemia (ALL) (Janssen et al.1985; Hirai et al. 1985). Activation of these genes has been associated with mutations in codons 12/13 or codon 61 and lesions of this type have recently been described in MDS. Hirai et al. (1987) described three MDS patients with codon 13 mutations in N-ras and Liu et al. (1987) two patients with a similar mutation in K-ras. We have assessed the mutational status of members of the ras gene family by polymerase chain reaction and hybridisation with synthetic oligonucleotide probes in 50 patients with MDS together with the use of a nude mouse tumorigenicity assay in some cases (Padua et al. 1988). We have also examined material from 70 haematologically normal patients in complete remission following cytotoxic therapy for lymphoma, but in whom a higher than normal incidence of MDS and leukaemia might be expected in subsequent years.

Keywords

Lymphoma Codon Valine Papilloma PASA 

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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • A. Jacobs
    • 1
    • 2
  • R. A. Padua
    • 1
    • 2
  • G. Carter
    • 1
    • 2
  • D. Hughes
    • 1
    • 2
  • R. E. Clark
    • 1
    • 2
  • D. Oscier
    • 1
    • 2
  • D. Bowen
    • 1
    • 2
  • J. F. McCormick
    • 1
    • 2
  1. 1.Cardiff, London, BournemouthUK
  2. 2.San FranciscoUSA

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