Genomic basis for RNA alterations in cancer

doi:10.1038/s41586-020-1970-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-1970-0
	Genomic basis for RNA alterations in cancer
	Petitprez, Florent 1; 39;han 2
	2020-01-15
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	578 期号:7793 页码:129-+
文章类型	Article
语种	英语
国家	England; Switzerland; USA; Singapore; Peoples R China; Japan; Canada; Scotland; Germany; Sweden
英文关键词	Transcript alterations often result from somatic changes in cancer genomes(1). Various forms of RNA alterations have been described in cancer, including overexpression(2), altered splicing(3) and gene fusions(4) however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)(5). Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed ' bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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:000529097800012
WOS关键词	R/BIOCONDUCTOR PACKAGE ; FUSION GENES ; R PACKAGE ; EXPRESSION ; IDENTIFICATION ; DNA ; MUTATIONS ; TRANSCRIPTOME ; ANNOTATION ; SIGNATURES
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/281349
专题	地球科学资源环境科学气候变化
作者单位	1.Univ Paris 05, INSERM, Ctr Rech Cordeliers, Team Canc Immune Control & Escape, Paris, France; 2.Univ Paris, Ctr Rech Cordeliers, Sorbonne Paris Cite, Paris, France; 3.Sorbonne Univ, Ctr Rech Cordeliers, Paris, France; 4.Ligue Natl Canc, Programme Cartes Ident Tumeurs, Paris, France; 5.Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA; 6.Natl Taiwan Univ, Grad Inst Oncol, Coll Med, Taipei, Taiwan; 7.Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan; 8.Natl Taiwan Univ, Canc Ctr, Taipei, Taiwan; 9.Natl Taiwan Univ, Ctr Genom & Precis Med, Taipei, Taiwan; 10.Grp Hosp Henri Mondor, AP HP, Dept Pathol, Creteil, France; 11.Inst Mondor Rech Biomed, Creteil, France; 12.Natl Taiwan Univ, Dept Pathol, Taipei, Taiwan; 13.Gustave Roussy, Dept Biol & Pathol, Villejuif, France; 14.Inst Bergonie, Bordeaux, France; 15.Inst Bergonie, Bioinformat Unit, Bordeaux, France; 16.Inst Bergonie, Dept Oncol, Bordeaux, France; 17.Univ Pittsburgh, Div Hematol Oncol, Dept Med, Pittsburgh, PA USA; 18.Canc Res & Biostat, Seattle, WA USA; 19.Sarcoma Alliance Res Collaborat, Ann Arbor, MI USA; 20.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA; 21.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA; 22.Univ Bordeaux, Bordeaux, France; 23.Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA
推荐引用方式 GB/T 7714	Petitprez, Florent,39;han. Genomic basis for RNA alterations in cancer[J]. NATURE,2020,578(7793):129-+.
APA	Petitprez, Florent,&39;han.(2020).Genomic basis for RNA alterations in cancer.NATURE,578(7793),129-+.
MLA	Petitprez, Florent,et al."Genomic basis for RNA alterations in cancer".NATURE 578.7793(2020):129-+.