Journal article
Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients
A Kahles, KV Lehmann, NC Toussaint, M Hüser, SG Stark, T Sachsenberg, O Stegle, O Kohlbacher, C Sander, SJ Caesar-Johnson, JA Demchok, I Felau, M Kasapi, ML Ferguson, CM Hutter, HJ Sofia, R Tarnuzzer, Z Wang, L Yang, JC Zenklusen Show all
Cancer Cell | CELL PRESS | Published : 2018
Abstract
Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified ≈930 exon-exon junctions (“neojunctions”) in tumors not typically f..
View full abstractGrants
Awarded by Merck
Funding Acknowledgements
We would like to thank the ICGC/PCAWG Transcriptome Working Group (in particular, Angela Brooks and Yuichi Shiraishi), Mitch Levesque, Mark Rubin, Ruedi Aebersold, Alessandra Curioni, Michal Bassani-Sternberg, George Coukos, and Nikolaus Schultz for fruitful discussions and feedback on project design, specific methods, and the manuscript. We also gratefully acknowledge the thorough review by the reviewers that has led to significant improvements of the manuscript. Data used in this publication were generated by the CPTAC (NCI/NIH). O. K. and T. S. acknowledge support from BMBF 031A535A. This work was funded by MSKCC core funding, ETH Zurich core funding to G. R., and SFA PHRT project grant PHRT #106 by the ETH Board to G. R.