Pan-cancer analysis of whole genomes.
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Publication Date
2020-02-05ICR Author
Author
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Type
Journal Article
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Show full item recordAbstract
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<sup>1-3</sup>. 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<sup>4</sup>; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation<sup>5,6</sup>; analyses timings and patterns of tumour evolution<sup>7</sup>; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity<sup>8,9</sup>; and evaluates a range of more-specialized features of cancer genomes<sup>8,10-18</sup>.
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Licenseref URL
http://creativecommons.org/licenses/by/4.0/Version of record
Subject
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Telomere
Humans
Neoplasms
Telomerase
Reproducibility of Results
DNA Mutational Analysis
Information Dissemination
Genomics
Evolution, Molecular
Cell Proliferation
RNA Splicing
Mutagenesis
Mutation
Germ-Line Mutation
Oncogenes
Genome, Human
Female
Male
Promoter Regions, Genetic
High-Throughput Nucleotide Sequencing
Cloud Computing
Chromothripsis
Cellular Senescence
Research team
Oncogenetics
Stereotactic and Precision Body Radiotherapy
Language
eng
Date accepted
2019-12-11
License start date
2020-02-05
Citation
Nature, 2020, 578 (7793), pp. 82 - 93
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
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