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The pattern of mutational involvement of RAS genes in human hematologic
malignancies determined by DNA amplification and direct sequencing
HG Ahuja, A Foti, M Bar-Eli and MJ Cline
Department of Medicine, Jonsson Cancer Center, UCLA School of Medicine
90024-1678.
DNA from 161 patients with various forms of hematologic malignancies were
investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS
gene by direct sequencing of DNA amplified in vitro by the polymerase chain
reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene
were identified in 18 of the 161 patients. The relative frequencies of
N-RAS gene mutations in these hematologic disorders was as follows: acute
myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%;
myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of
chronic myelogenous leukemia (CML), 3%. No correlation was observed between
the presence of mutations and cytologic features or immunophenotype of
these malignancies. Mutations involving codons 12 or 13 were equally
prevalent, with a glycine to aspartic acid substitution being the most
frequently encountered change. A single T-ALL case had a codon 11 mutation
resulting in substitution of alanine with threonine. We failed to find
mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except
a single AML with a mutation in codon 61 of the K-RAS gene. Also, no
mutations were identified in chronic phase of CML, chronic lymphocytic
leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or
multiple myeloma. These results indicate that RAS mutations, especially
those involving exon 1 of the N-RAS gene, are frequent only in a subset of
hematologic malignancies.
Volume 75,
Issue 8,
pp. 1684-1690,
04/15/1990
Copyright © 1990 by The American Society of Hematology

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