Pan-cancer analysis of whole genomes

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, The (2020) Pan-cancer analysis of whole genomes. Nature, 578. pp. 82-93.

[img]
Preview
PDF (Published version) - Published Version
Available under License Creative Commons Attribution.

Download (23MB) | Preview
View at Publisher Website: https://doi.org/10.1038/s41586-020-1969-...
 
96
57


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 scale1–3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.

Item ID: 62307
Item Type: Article (Research - C1)
ISSN: 1476-4687
Copyright Information: © 2020 Springer Nature Limited. This is an Open Access article distributed under a Creative Commons Attribution license.
Additional Information:

Dr Matt Field (AITHM) is a member of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium.

Date Deposited: 26 Feb 2020 04:56
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060408 Genomics @ 50%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060102 Bioinformatics @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
Downloads: Total: 57
Last 12 Months: 16
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page