Landscape of Drug Resistance Mutations in Cancer

CRISTINA MARINO BUSLE; ELIZABETH MARTÍNEZ-PÉREZ

Posadas, Misiones

Congreso; VIII congreso de la Asoc. Arg. de Bioinformática y Biol Comp; 2017

Asoc. Arg. de Bioinformática y Biol Comp

BackgroundResistance to targeted drug treatment appears in some patients following an initial drug response. Acquired resistance occurs within the tumour where subpopulations of cells may acquire or already have the mutations enabling them to emerge under selective pressure. The Catalog of Somatic Mutations in Cancer (COSMIC) begun to annotate mutations identified in the literature as resistant, including those post-treatment and intrinsic resistance. In this work, we present an structural analysis of mutations conferring drug resistance.ResultsWe retrieved drug-resistance mutations from Cosmic. The analysis include 1675 samples with 1817 mutations (119 unique) belonging to 11 proteins, 8 of which are kinases.For kinases, We aligned them and mapped the mutations onto FLT3 in order to inspect their distribution. Some positions are mutated in many samples and also appear in many kinases: e.g FLT3.F691 (equivalent to EGFR.T790) has 483 mutated samples among 5 kinases. While others are mutated in many samples but are kinase specific: e.g ABL1.E255 has 97 samples and is the only kinase having this position mutated (located in the equivalent position K623 in FLT3). 42.3% of the mutated positions lay near the drug binding site (