Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- PMID: 32025015
- PMCID: PMC7054214
- DOI: 10.1038/s41586-020-1965-x
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
Erratum in
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Author Correction: Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.Nature. 2023 Feb;614(7948):E40. doi: 10.1038/s41586-022-05599-9. Nature. 2023. PMID: 36697832 Free PMC article. No abstract available.
Abstract
The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
Conflict of interest statement
The following authors declare that they have competing interests. P.B. receives grant funding from Novartis from an unrelated project; R.B. owns equity in Ampressa Therapeutics and receives grant funding from Novartis; G.G. receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER; B.J.R. is a consultant at and has ownership interest (including stock, patents and so on) in Medley Genomics; O.S. is currently an employee of Cedilla Therapeutics); and Y.L. is currently an employee of Seven Bridges Genomics.
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Comment in
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Global genomics project unravels cancer's complexity at unprecedented scale.Nature. 2020 Feb;578(7793):39-40. doi: 10.1038/d41586-020-00213-2. Nature. 2020. PMID: 32025004 No abstract available.
References
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- The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network. Pan-cancer analysis of whole genomes. Nature 10.1038/s41586-020-1969-6 (2020).
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