Pan-cancer analysis of whole genomes

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation; analyses timings and patterns of tumour evolution; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity; and evaluates a range of more-specialized features of cancer genomes.

Detaljer

Författare
  • Peter J. Campbell
  • Dorthe Grabau (Medarbetare)
  • Åke Borg (Medarbetare)
  • Markus Ringnér
  • Anna Ehinger (Medarbetare)
  • Jiashan Zhang
  • The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • National Cancer Institute
  • Wellcome Trust Sanger Institute
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
  • Cancer och onkologi
Originalspråkengelska
Sidor (från-till)82-93
TidskriftNature
Volym578
StatusPublished - 2020 feb 5
PublikationskategoriForskning
Peer review utfördJa

Relaterade aktiviteter

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