Pan-cancer study of heterogeneous RNA aberrations

Pan-cancer studies have transformed our understanding of recurrent somatic mutations that contribute to cancer pathogenesis; however, there has yet to be a full investigation of the multiple mechanisms in which genes can be somatically altered, particularly at the transcriptomelevel. We present the most comprehensive catalogue of cancer-associated gene alterations through extensive characterization of tumor transcriptomesfrom 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project with matched whole-genome sequencedata. We processed the RNA-seqdata with a unified analysis pipeline that included both sequence alignmentand extensive quality control. Subsequently, we identified gene alterations through gene expression, alternative splicing, alternative transcription starts, allele-specific expression, RNA-editedsites, and gene fusions, and by comparing with RNA-Seqfrom a panel of normal tissue samples from the Genotype-Tissue Expression (GTEx) project. Our data represent an extensive pan-cancer catalog of RNA-level aberrations for each gene and will be the basis for further analyses within PCAWG. NOTE TO READERS: This is a draft of a marker paper from the PCAWG TranscriptomeWorking Group and is intended to describe technical aspects of RNA-Seqanalysis associated with the PCAWG project. The full marker paper is currently in preparation.