Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

doi:10.1038/s41586-020-1965-x

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-1965-x
	Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
	Clark, Timothy D.1; Raby, Graham D.2; Roche, Dominique G.3,4,5; Binning, Sandra A.4,5; Speers-Roesch, Ben 6; Jutfelt, Fredrik 7; Sundin, Josefin 7,8,9
	2020-01-16
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	578 期号:7793 页码:102-+
文章类型	Article
语种	英语
国家	USA; Denmark; England; Germany; Spain; Canada; Switzerland; Japan; Sweden; South Korea; Poland; Estonia; Australia; Italy; Belgium; Norway; Peoples R China; Israel; Russia; Scotland
英文关键词	The discovery of drivers of cancer has traditionally focused on protein-coding genes(1-4). 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) Consortium(5) 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 drivers(6,7), 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.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000529097800009
WOS关键词	TERT PROMOTER MUTATIONS ; REGULATORY MUTATIONS ; RECURRENT ; GENES ; DISCOVERY ; LANDSCAPE ; TARGET ; ANNOTATION ; EXPRESSION ; SELECTION
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281220
专题	地球科学资源环境科学气候变化
作者单位	1.Deakin Univ, Sch Life & Environm Sci, Geelong, Vic, Australia; 2.Univ Windsor, Great Lakes Inst Environm Res, Windsor, ON, Canada; 3.Carleton Univ, Dept Biol, Ottawa, ON, Canada; 4.Univ Neuchatel, Inst Biol, Ecoethol, Neuchatel, Switzerland; 5.Univ Montreal, Dept Sci Biol, Montreal, PQ, Canada; 6.Univ New Brunswick, Dept Biol Sci, St John, NB, Canada; 7.Norwegian Univ Sci & Technol, Dept Biol, Trondheim, Norway; 8.Uppsala Univ, Dept Neurosci, Uppsala, Sweden; 9.Swedish Univ Agr Sci, Dept Aquat Resources, Drottningholm, Sweden
推荐引用方式 GB/T 7714	Clark, Timothy D.,Raby, Graham D.,Roche, Dominique G.,et al. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes[J]. NATURE,2020,578(7793):102-+.
APA	Clark, Timothy D..,Raby, Graham D..,Roche, Dominique G..,Binning, Sandra A..,Speers-Roesch, Ben.,...&Sundin, Josefin.(2020).Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.NATURE,578(7793),102-+.
MLA	Clark, Timothy D.,et al."Analyses of non-coding somatic drivers in 2,658 cancer whole genomes".NATURE 578.7793(2020):102-+.