Pan-cancer analysis of whole genomes.

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Collaborators (2020). Pan-cancer analysis of whole genomes. Nature, 578(7793), pp. 82-93. Springer Nature 10.1038/s41586-020-1969-6

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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 Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-4687

Publisher:

Springer Nature

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

08 Jun 2020 11:06

Last Modified:

14 Jun 2020 02:51

Publisher DOI:

10.1038/s41586-020-1969-6

PubMed ID:

32025007

Additional Information:

Rory Johnson ist Collaborator bei ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium

BORIS DOI:

10.7892/boris.143032

URI:

https://boris.unibe.ch/id/eprint/143032

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