Synapse - Pan-cancer analysis of whole genomes

Pan-cancer analysis of whole genomes Journal Article

Author:	The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Contributors:	Yellapantula, V. D.; Rätsch, G.; Kahles, A.; Lehmann, K. V.; Davidson, N. R.; Stark, S. G.; Larsson, E.; Liu, E. M.; Sander, C.; Vázquez-García, I.; Roehrl, M. H. A.; Giri, D. D.; King, T. A.; Reis-Filho, J.; Gundem, G.; Abeshouse, A.; Al-Ahmadie, H.; Armenia, J.; Chen, H. W.; Gao, J.; Ghossein, R.; Heines, Z.; Huse, J.; Iacobuzio-Donahue, C. A.; Kundra, R.; Levine, D. A.; Ochoa, A.; Pastore, A.; Reuter, V.; Sanchez-Vega, F.; Schultz, N.; Senbabaoglu, Y.; Singer, S.; Socci, N. D.; Zhang, H.
Article Title:	Pan-cancer analysis of whole genomes
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. © 2020, The Author(s).
Keywords:	promoter region; single nucleotide polymorphism; somatic mutation; gene deletion; mutation; janus kinase 2; nonhuman; gene; dna repair; gene expression profiling; epidermal growth factor receptor; genetic variability; tumor suppressor gene; telomerase reverse transcriptase; genomics; genome; cyclin dependent kinase inhibitor 2a; egfr gene; point mutation; transcription factor sox2; protein mdm2; oncogene ret; daxx protein; germline mutation; cdkn2a gene; jak2 gene; rb1 gene; mdm2 gene; sox2 gene; atrx gene; chromothripsis; daxx gene; setd2 gene; tert gene; ccnd1 gene; cancer; human; priority journal; article; whole genome sequencing; malignant neoplasm; transcriptional regulator atrx; apobec3b gene; igf2bp3 gene
Journal Title:	Nature
Volume:	578
Issue:	7793
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Date Published:	2020-02-06
Start Page:	82
End Page:	93
Language:	English
DOI:	10.1038/s41586-020-1969-6
PUBMED:	32025007
PROVIDER:	scopus
PMCID:	PMC7025898
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079038817&doi=10.1038%2fs41586-020-1969-6&partnerID=40&md5=14a30f74e616a8d4dbdfddefb9fd4c08
Notes:	Erratum issued, see DOI: 10.1038/s41586-022-05598-w -- Article -- Export Date: 2 March 2020 -- Source: Scopus