RAS MUTATIONS IN MYELODYSPLASIA DETECTED BY AMPLIFICATION, OLIGONUCLEOTIDE HYBRIDIZATION, AND TRANSFORMATION

Google Scholar
  • 1 August 1988
    • journal article
    • research article
    • Vol. 2  (8) , 503-510
Abstract
Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation fo H, K, and NRAS in myelodysplsia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progessed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results sow that RAS mutation can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations apepars to be significantly higher in CMML than in the other subgroups (p = 0.02).