title: Molecular analysis of WT1 and KIT mutations in patients from an Indian population with de novo acute myeloid leukemia: determination of incidence, distribution patterns, and report of a novel KIT mutation.
abstract: Mutations of the WT1 gene have been reported as the most common abnormality after NPM1 and FLT3 gene mutations in acute myeloid leukemia (AML), while KIT mutations are predominantly found in core-binding factor (CBF) AMLs. We report for the first time the prevalence and distribution patterns of WT1 and KIT mutations in an Indian population of 150. Overall, 10 (6.7%) and four (2.7%) of the cases had WT1 and KIT mutations, respectively. Of the six mutations observed in exon 7, five were frameshift while the remaining one case showed a substitution mutation. In contrast to exon 7, no frameshift mutation was detected in exon 9, where all mutations were substitution mutations. Interestingly, we observed a novel mutation in exon 8 of the KIT gene resulting from the deletion of nine nucleotides and insertion of three nucleotides affecting the extracellular domain of the KIT receptor, while Asp816Tyr and Asp816His were commonly found in exon 17 of the KIT gene. The WT1 mutation was more prevalent in normal karyotype AML while KIT was associated with t(8;21). With respect to FLT3 and NPM1 mutations, WT1 was more predominant in FLT3 positive cases and less in NPM1 mutation cases, while no KIT mutation was found in FLT3/NPM1 positive cases.
authors.affiliation: Research and Development Division, Super Religare Laboratories Ltd., Mumbai, India.
authors.forename: Firoz
authors.initials: F
authors.lastname: Ahmad
authors.forename: Wilma
authors.initials: W
authors.lastname: D'Souza
authors.forename: Swarna
authors.initials: S
authors.lastname: Mandava
authors.forename: Bibhu Ranjan
authors.initials: BR
authors.lastname: Das
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D025721:WT1 Proteins; D000090243:Nucleophosmin; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3