Tumor profiling from whole-genome and whole transcriptome sequencing to uncover gene fusions and structural variations in clinically relevant cancer genes.

e23118Background: Current targeted cancer therapies rely on the identification of clinically relevant somatic alterations in the tumor. Hotspot gene-panels and exome sequencing are designed to quickly assess somatic variations in frequently mutated regions and/or the coding regions of relevant genes, but they have limited ability to detect complex genomic rearrangements or novel structural variations. Here, we describe an integrative and comprehensive approach to fully characterize the genomic complexity of solid tumors using high throughput whole genome sequencing (WGS) and whole transcriptome sequencing (RNA Seq). Methods: We performed WGS and high-depth sequencing of known cancer genes in 14 paired tumor-normal samples of a variety of tumor types. Tumor-specific somatic alteration assessments included protein-coding mutations, copy number variations, gene fusions and structural variants. In addition, RNA Seq data was analyzed to identify expressed somatic alterations. Results: We identified 2 novel fus...