TY - JOUR T1 - Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types JF - bioRxiv DO - 10.1101/183889 SP - 183889 AU - PCAWG Transcriptome Core Group AU - Claudia Calabrese AU - Natalie R. Davidson AU - Nuno A. Fonseca AU - Yao He AU - André Kahles AU - Kjong-Van Lehmann AU - Fenglin Liu AU - Yuichi Shiraishi AU - Cameron M. Soulette AU - Lara Urban AU - Deniz Demircioğlu AU - Liliana Greger AU - Siliang Li AU - Dongbing Liu AU - Marc D. Perry AU - Linda Xiang AU - Fan Zhang AU - Junjun Zhang AU - Peter Bailey AU - Serap Erkek AU - Katherine A. Hoadley AU - Yong Hou AU - Helena Kilpinen AU - Jan O. Korbel AU - Maximillian G. Marin AU - Julia Markowski AU - Tannistha Nandi AU - Qiang Pan-Hammarström AU - Chandra Sekhar Pedamallu AU - Reiner Siebert AU - Stefan G. Stark AU - Hong Su AU - Patrick Tan AU - Sebastian M. Waszak AU - Christina Yung AU - Shida Zhu AU - PCAWG Transcriptome Working Group AU - Philip Awadalla AU - Chad J. Creighton AU - Matthew Meyerson AU - B.F. Francis Ouellette AU - Kui Wu AU - Huangming Yang AU - ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network AU - Alvis Brazma AU - Angela N. Brooks AU - Jonathan Göke AU - Gunnar Rätsch AU - Roland F. Schwarz AU - Oliver Stegle AU - Zemin Zhang Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/12/183889.abstract N2 - We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called “bridged” fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations. ER -