DNMT3A Co-Mutation with SF3B1, ASXL1 and TET2 in Indian Patients with Myelodysplastic Syndrome (MDS)

Abstract

Myelodysplastic syndrome (MDS) encompasses a diverse group of closely related clonal hematopoietic disorders.Several genes are often mutated in MDS, of which only five (DNMT3A, SF3B1, ASXL1, TET2 and SRSF2) are known to be mutated in >10% of cases. In this perspective, we studied the frequency of somatic mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes and also the impact of DNMT3A co-mutation with SF3B1, ASXL1 and TET2 genes in a series of 21 Indian patients primarily diagnosed with MDS. Patients with de novo MDS were examined for mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes by Sanger's sequencing. The prognostic impact of DNMT3A mutations was evaluated in juxtaposition with SF3B1, ASXL1 and TET2 gene. Around 62% patients (13 out of 21) were found to have a somatic mutation in at least one of the genes studied herein. Of the 13 patients, 2 patients had single mutation of DNMT3A, 5 carried SF3B1 mutation and one patient each had ASXL1 and TET2 mutation. Likewise, 2 patients carried double mutation of DNMT3A/TET2 and one each carried DNMT3A/SF3B1 and DNMT3A/ASXL1 co-mutation. Our study identified novel missense, nonsense and frameshift mutations in DNMT3A, SF3B1, ASXL1 and TET2 genes for the first time in Indian MDS patients. Distinct mutations of DNMT3A in juxtaposition with SF3B1, ASXL1 and TET2 gene were predictive of clinical status.