RNA interference identification of relevant novel mutations detected by next generation sequencing in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a genetically complex leukemia caused by accumulation of various genetic defects that affect critical cellular functions such as proliferation, survival, differentiation, cell cycle and self-renewal. Despite the multiplicity of known mutations, our knowledge of the genetics of T-ALL still seems incomplete. Recent developments in sequencing technologies (next generation sequencing) now enable sequence analysis of entire cancer exomes, transciptomes and even entire cancer genomes with unprecedented speed and at relatively low cost. We are currently performing whole exome and transcriptome sequencing of T-ALL samples to extend our understanding of the molecular pathogenesis of T-ALL. These sequencing techniques however detect both driver mutations that directly contribute to cancer development as well as passenger mutations that were accidently fixed in the cancer genome. In order to identify gain-of-function driver mutations from our list of candidate T-ALL associated sequence variants, we will apply RNA interference technology so that we can select the mutated molecules that are required for survival and proliferation of T-ALL cells.

Keywords:RNA interference technology, Cancer, Next generation sequencing, Driver mutations, Leukemia.

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences