Protein Expression By Genetic Mutations Identified In Gene Panels (Hotspots) And Efficacy Of Targeted Treatments.

JOURNAL OF CLINICAL ONCOLOGY(2015)

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Abstract
11005 Background: Treatment decision support by next generation sequencing of gene panels is currently limited to the analysis of somatic (tumor) data from DNA sequencing without taking into consideration expression of mutated genes. We present here a supercomputer-driven, cloud-based integrated analysis of genomic (DNA) and transcriptomic (RNA) sequencing data to 1) directly identify driver variants between somatic and germline (normal) DNA and 2) to determine expression of identified mutations in a cohort of 3,784 patients, thereby establishing therapeutic relevance of the mutated genes overcoming the limitations of panels. Methods: This large scale 3,784 patient genomic (DNA and RNA sequencing) data set from 19 anatomical tumor types was processed to detect DNA variants (germline vs somatic) and RNA expression, and to establish not only the existence but also the expression level of hotspot mutations in the following oncogenes: PIK3CA, KRAS, NRAS, AKT1, BRAF, IDH1, CTNNB1, and IDH2. Results: Of the 3,7...
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Key words
protein expression,genetic panels,genetic mutations
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