title: Analysis of RAS gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes.
abstract: 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 acid 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.
authors.affiliation: Institute of Cancer Research, Royal Cancer Hospital, Chester Beatty Laboratories, London, England.
authors.forename: C J
authors.initials: CJ
authors.lastname: Farr
authors.forename: R K
authors.initials: RK
authors.lastname: Saiki
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
authors.forename: F
authors.initials: F
authors.lastname: McCormick
authors.forename: C J
authors.initials: CJ
authors.lastname: Marshall
mesh_terms: D004273:DNA, Neoplasm / Q000235:genetics*; D011905:Genes, ras; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009693:Nucleic Acid Hybridization
chemical_list: D004273:DNA, Neoplasm