Back
Full-text
Journal article

Genomic basis for RNA alterations in cancer.

  • Calabrese C ETH Zurich, Zurich, Switzerland.
  • Davidson NR National University of Singapore, Singapore, Singapore.
  • Demircioğlu D European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Fonseca NA Peking University, Beijing, China.
  • He Y ETH Zurich, Zurich, Switzerland.
  • Kahles A ETH Zurich, Zurich, Switzerland.
  • Lehmann KV Peking University, Beijing, China.
  • Liu F The University of Tokyo, Minato-ku, Japan.
  • Shiraishi Y University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Soulette CM European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Urban L European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Greger L BGI-Shenzhen, Shenzhen, China.
  • Li S BGI-Shenzhen, Shenzhen, China.
  • Liu D Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Perry MD Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Xiang Q Peking University, Beijing, China.
  • Zhang F Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Zhang J University of Glasgow, Glasgow, UK.
  • Bailey P European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
  • Erkek S The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hoadley KA BGI-Shenzhen, Shenzhen, China.
  • Hou Y Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
  • Huska MR University College London, London, UK.
  • Kilpinen H European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
  • Korbel JO University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Marin MG Berlin Institute for Medical Systems Biology, Max Delbruck Center for Molecular Medicine, Berlin, Germany.
  • Markowski J Genome Institute of Singapore, Singapore, Singapore.
  • Nandi T BGI-Shenzhen, Shenzhen, China.
  • Pan-Hammarström Q Broad Institute, Cambridge, MA, USA.
  • Pedamallu CS Ulm University and Ulm University Medical Center, Ulm, Germany.
  • Siebert R ETH Zurich, Zurich, Switzerland.
  • Stark SG BGI-Shenzhen, Shenzhen, China.
  • Su H Genome Institute of Singapore, Singapore, Singapore.
  • Tan P European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
  • Waszak SM Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Yung C BGI-Shenzhen, Shenzhen, China.
  • Zhu S Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Awadalla P Baylor College of Medicine, Houston, TX, USA.
  • Creighton CJ Broad Institute, Cambridge, MA, USA.
  • Meyerson M University of Toronto, Toronto, Ontario, Canada.
  • Ouellette BFF BGI-Shenzhen, Shenzhen, China.
  • Wu K BGI-Shenzhen, Shenzhen, China.
  • Yang H European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Brazma A Genome Institute of Singapore, Singapore, Singapore.
  • Brooks AN ETH Zurich, Zurich, Switzerland. raetsch@inf.ethz.ch.
  • Göke J European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Rätsch G European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, UK.
  • Schwarz RF Peking University, Beijing, China.
  • Stegle O
  • Zhang Z
Show more…
  • 2020-02-07
Published in:
  • Nature. - 2020
DNA Copy Number Variations
DNA, Neoplasm
Gene Expression Regulation, Neoplastic
Genome, Human
Genomics
Humans
Neoplasms
RNA
Transcriptome
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/99334
Statistics
Document views: 10 File downloads:
  • fulltext.pdf: 0