Genomic basis for RNA alterations in cancer.
Authors
PCAWG Transcriptome Core Group
Calabrese, Claudia
Davidson, Natalie R
Demircioğlu, Deniz
Fonseca, Nuno A
He, Yao
Kahles, André
Lehmann, Kjong-Van
Liu, Fenglin
Shiraishi, Yuichi
Soulette, Cameron M
Urban, Lara
Greger, Liliana
Li, Siliang
Liu, Dongbing
Perry, Marc D
Xiang, Qian
Zhang, Fan
Zhang, Junjun
Bailey, Peter
Erkek, Serap
Hoadley, Katherine A
Hou, Yong
Huska, Matthew R
Kilpinen, Helena
Korbel, Jan O
Marin, Maximillian G
Markowski, Julia
Nandi, Tannistha
Pan-Hammarström, Qiang
Pedamallu, Chandra Sekhar
Siebert, Reiner
Stark, Stefan G
Su, Hong
Tan, Patrick
Waszak, Sebastian M
Yung, Christina
Zhu, Shida
Awadalla, Philip
Creighton, Chad J
Meyerson, Matthew
Ouellette, BF Francis
Wu, Kui
Yang, Huanming
PCAWG Transcriptome Working Group
Brazma, Alvis
Brooks, Angela N
Göke, Jonathan
Rätsch, Gunnar
Schwarz, Roland F
Stegle, Oliver
Zhang, Zemin
PCAWG Consortium
Publication Date
2020-02Journal Title
Nature
ISSN
0028-0836
Publisher
Springer Science and Business Media LLC
Volume
578
Issue
7793
Pages
129-136
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
PCAWG Transcriptome Core Group, Calabrese, C., Davidson, N. R., Demircioğlu, D., Fonseca, N. A., He, Y., Kahles, A., et al. (2020). Genomic basis for RNA alterations in cancer.. Nature, 578 (7793), 129-136. https://doi.org/10.1038/s41586-020-1970-0
Abstract
Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
Keywords
Article, /631/67/69, /631/114/2401, /38/23, /38/91, article
Identifiers
s41586-020-1970-0, 1970
External DOI: https://doi.org/10.1038/s41586-020-1970-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317164
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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