Frequency of RAS gene mutation and its cooperative genetic events in Southeast Asian adult acute myeloid leukemia.
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AbstractRAS gene as one of the most frequently mutated genes in acute myeloid leukemia (AML) has become an attractive target for molecular therapy. The role of oncogenic RAS and its associated genetic events in AML are not yet defined. We examined the frequency of RAS mutation in 239 Thai de novo adult AML patients using polymerase chain reaction-single-strand conformational polymorphism analysis. Thirty-five RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 subtype (38%). Ten cases were positive for N-RAS codon 12, 11 cases for N-RAS codon 61, 13 cases for N-RAS codon 13, and one case for K-RAS codon 13. No mutation was found in K-RAS exon 2 or H-RAS. The most common base substitution was the G to A transition at codon 13. Most M1/M2 cases had mutations at codon 12 or 13, whereas M4/M5 cases preferentially affected codon 61. Half of the patients with RAS mutations had abnormal karyotypes with the majority involving chromosomes 21, 11 and 7. Four patients had core-binding factor leukemia and four additional patients had coexisting FLT3 or AML1 mutation. One patient had RAS, FLT3 and t(8;21) and the other had RAS, AML1 point mutation and del(9q). In conclusion, mutation of RAS gene was not as common in the Thais as in the western population. Several additional genetic abnormalities occurred in RAS-mutated patients. Future molecular-targeting approaches should take into account the multiple genetic events that coexist with RAS mutations in AML patients.
CitationEur. J. Haematol. 2006, 77 (1):51-56 Eur. J. Haematol.
JournalEuropean journal of haematology
DescriptionBiomarkers of individual susceptibility: field studiesBiomarker (including alleles if genetic): N-RAS, K-RAS, H-RASEffect studied (phenotype/pathology):frequency and type of RAS mutationsMethod of analysis: PCR-SSCPStudy design: cross-sectionalStudy size: 239 Thai adult AML patientsImpact on outcome (including dose-response):10/239 N-RAS codon 12, 13/239 N-RAS codon 13, 11 N-RAS codon 61, 1/239 K-RAS codon 13Correlation with other biomarkers: 2 of 239 cases had coexistent FLT3 and RAS mutations. Keywords classification: abnormalities;analysis;Acute Disease;Adult;Asia,Southeastern;biomarkers of exposure & effect: field studies;classification;Codon;Core Binding Factor Alpha 2 Subunit;DNA Mutational Analysis;epidemiology;Epidemiology,Molecular;field studies;fms-Like Tyrosine Kinase 3;Female;genetics;Gene Frequency;Humans;Leukemia,Myeloid;Male;Mutation;Proteins;ras Proteins;Research;therapy;Thailand;Tyrosine;genetic;