Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types
PCAWG Transcriptome Core Group,
Natalie R Davidson,
Nuno A. Fonseca,
Cameron M. Soulette,
Marc D. Perry,
Katherine A. Hoadley,
Jan O. Korbel,
Maximillian G. Marin,
Chandra Sekhar Pedamallu,
Stefan G Stark,
Sebastian M. Waszak,
PCAWG Transcriptome Working Group,
Chad J. Creighton,
B.F. Francis Ouellette,
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network,
Angela N. Brooks,
Roland F. Schwarz,
Posted 03 Sep 2017
bioRxiv DOI: 10.1101/183889
Posted 03 Sep 2017
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.
- Downloaded 3,992 times
- Download rankings, all-time:
- Site-wide: 1,203 out of 94,912
- In genomics: 246 out of 5,955
- Year to date:
- Site-wide: 8,065 out of 94,912
- Since beginning of last month:
- Site-wide: 22,487 out of 94,912
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!