Analysis of RAS Gene Mutations in Acute Myeloid Leukemia by Polymerase Chain Reaction and Oligonucleotide Probes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 5; pp. 1629 - 1633
• Main Authors: Farr, Christine J., Saiki, Randall K., Erlich, Henry A., McCormick, Frank, Marshall, Christopher J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.03.1988; National Acad Sciences
• Subjects: Alleles; Codons; DNA probes; DNA, Neoplasm - genetics; Genes, ras; Genetic mutation; Genetic screening; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Mutation; Myeloid leukemia; Nucleic Acid Hybridization; Oligonucleotide probes; Polymerase chain reaction; ras genes; Relapse
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.5.1629

In vitro DNA amplification followed by oligonucleotide dot blot analysis were used to study RAS gene mutations in acute myeloid leukemia (AML). Fifty-two presentation AML DNAs were screened for mutations in codons 12, 13, and 61 of NRAS and in codons 12 and 61 of KRAS and HRAS. Fourteen (27%) contained mutations--all in NRAS and predominantly in codon 12. The most common amino acid substitution identified was of glycine by aspartic at codon 12 (7/18), with a G → A transition being the most common base change (11/18). No particular correlation was observed between disease subtype and the incidence or type of NRAS mutation. In DNA samples from four patients, 2 NRAS mutations were found to coexist. NIH 3T3 focus-formation assays revealed that in each case the mutations were present in different NRAS alleles. We also report the absence of a mutated RAS gene in relapse DNAs of four patients in which a RAS oncogene had been detected at presentation. These observations suggest that RAS mutations arise as part of the evolution of neoplastic transformation.