Identification of Novel Insertions and Deletions in Haematopoietic Stem/Progenitor Cells in de novo Myelodysplastic Syndromes.

Myelodysplastic Syndromes (MDS) are . The molecular basis of MDS is heterogeneous and the molecular mechanisms underlying biology of this complex disorder are not fully understood. Genetic variations (GVs) occur in about 90% of patients with MDS. It has been shown that in addition to the single nucleotide variations, insertions and deletions (indels) in the key genes that are known to drive MDS, could also play a role in pathogenesis of MDS. However, only a few genetic studies have analyzed indels in MDS. The present study reports indels of bone marrow (BM) derived CD34 haematopoietic stem/progenitor cells of 20 newly diagnosed MDS patients using next generation sequencing.A total of 88 indels (9 insertions and 79 deletions) across 28 genes were observed. The genes that showed more than five indels are (N=6), (N=6), (N=8), (N=9), (N=9) and (N=10). Deletion in the gene (c.3957_3959delGGA, TGAG>TGAG/T) was the most recurrent deletion and was observed in 4/20 patients. The other recurrent deletions reported were (W15X, N=2) and (G274X, N=3). The recurrent insertions were detected in the (E598DYVDFREYE, N=3) and in the (L287LCX, N=3) genes. The findings of this study may have a diagnostic, prognostic and a therapeutic value for MDS after validation using a larger cohort.