000153599 001__ 153599 000153599 005__ 20240229123045.0 000153599 0247_ $$2doi$$a10.1038/s41586-020-1970-0 000153599 0247_ $$2pmid$$apmid:32025019 000153599 0247_ $$2ISSN$$a0028-0836 000153599 0247_ $$2ISSN$$a1476-4687 000153599 0247_ $$2altmetric$$aaltmetric:75079052 000153599 037__ $$aDKFZ-2020-00343 000153599 041__ $$aeng 000153599 082__ $$a500 000153599 1001_ $$aGroup, PCAWG Transcriptome Core$$b0$$eCollaboration Author 000153599 245__ $$aGenomic basis for RNA alterations in cancer. 000153599 260__ $$aLondon [u.a.]$$bNature Publ. Group52462$$c2020 000153599 3367_ $$2DRIVER$$aarticle 000153599 3367_ $$2DataCite$$aOutput Types/Journal article 000153599 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1675070892_23510 000153599 3367_ $$2BibTeX$$aARTICLE 000153599 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000153599 3367_ $$00$$2EndNote$$aJournal Article 000153599 520__ $$aTranscript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; 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. 000153599 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000153599 588__ $$aDataset connected to CrossRef, PubMed, 000153599 7001_ $$aCalabrese, Claudia$$b1 000153599 7001_ $$aDavidson, Natalie R$$b2 000153599 7001_ $$aDemircioğlu, Deniz$$b3 000153599 7001_ $$aFonseca, Nuno A$$b4 000153599 7001_ $$aHe, Yao$$b5 000153599 7001_ $$aKahles, André$$b6 000153599 7001_ $$aLehmann, Kjong-Van$$b7 000153599 7001_ $$aLiu, Fenglin$$b8 000153599 7001_ $$aShiraishi, Yuichi$$b9 000153599 7001_ $$aSoulette, Cameron M$$b10 000153599 7001_ $$aUrban, Lara$$b11 000153599 7001_ $$aGreger, Liliana$$b12 000153599 7001_ $$aLi, Siliang$$b13 000153599 7001_ $$aLiu, Dongbing$$b14 000153599 7001_ $$aPerry, Marc D$$b15 000153599 7001_ $$aXiang, Qian$$b16 000153599 7001_ $$aZhang, Fan$$b17 000153599 7001_ $$aZhang, Junjun$$b18 000153599 7001_ $$aBailey, Peter$$b19 000153599 7001_ $$aErkek, Serap$$b20 000153599 7001_ $$aHoadley, Katherine A$$b21 000153599 7001_ $$aHou, Yong$$b22 000153599 7001_ $$aHuska, Matthew R$$b23 000153599 7001_ $$aKilpinen, Helena$$b24 000153599 7001_ $$aKorbel, Jan O$$b25 000153599 7001_ $$aMarin, Maximillian G$$b26 000153599 7001_ $$aMarkowski, Julia$$b27 000153599 7001_ $$aNandi, Tannistha$$b28 000153599 7001_ $$aPan-Hammarström, Qiang$$b29 000153599 7001_ $$aPedamallu, Chandra Sekhar$$b30 000153599 7001_ $$aSiebert, Reiner$$b31 000153599 7001_ $$aStark, Stefan G$$b32 000153599 7001_ $$aSu, Hong$$b33 000153599 7001_ $$aTan, Patrick$$b34 000153599 7001_ $$aWaszak, Sebastian M$$b35 000153599 7001_ $$aYung, Christina$$b36 000153599 7001_ $$aZhu, Shida$$b37 000153599 7001_ $$aAwadalla, Philip$$b38 000153599 7001_ $$aCreighton, Chad J$$b39 000153599 7001_ $$aMeyerson, Matthew$$b40 000153599 7001_ $$aOuellette, B F Francis$$b41 000153599 7001_ $$aWu, Kui$$b42 000153599 7001_ $$aYang, Huanming$$b43 000153599 7001_ $$aGroup, PCAWG Transcriptome Working$$b44$$eCollaboration Author 000153599 7001_ $$aBrazma, Alvis$$b45 000153599 7001_ $$aBrooks, Angela N$$b46 000153599 7001_ $$aGöke, Jonathan$$b47 000153599 7001_ $$aRätsch, Gunnar$$b48 000153599 7001_ $$0P:(DE-HGF)0$$aSchwarz, Roland F$$b49 000153599 7001_ $$0P:(DE-He78)9aabcfee1a1fc9202398a45a63f0b1e3$$aStegle, Oliver$$b50$$eLast author 000153599 7001_ $$aZhang, Zemin$$b51 000153599 7001_ $$aConsortium, PCAWG$$b52$$eCollaboration Author 000153599 7001_ $$aCalabrese, Claudia$$b53 000153599 7001_ $$aDavidson, Natalie R$$b54 000153599 7001_ $$aDemircioğlu, Deniz$$b55 000153599 7001_ $$aFonseca, Nuno A$$b56 000153599 7001_ $$aHe, Yao$$b57 000153599 7001_ $$aKahles, André$$b58 000153599 7001_ $$aLehmann, Kjong-Van$$b59 000153599 7001_ $$aLiu, Fenglin$$b60 000153599 7001_ $$aShiraishi, Yuichi$$b61 000153599 7001_ $$aSoulette, Cameron M$$b62 000153599 7001_ $$aUrban, Lara$$b63 000153599 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$$aFrenkel-Morgenstern, Milana$$b89 000153599 7001_ $$aGoldman, Mary$$b90 000153599 7001_ $$aHoadley, Katherine A$$b91 000153599 7001_ $$aHou, Yong$$b92 000153599 7001_ $$aHuska, Matthew R$$b93 000153599 7001_ $$aKhurana, Ekta$$b94 000153599 7001_ $$aKilpinen, Helena$$b95 000153599 7001_ $$aKorbel, Jan O$$b96 000153599 7001_ $$aLamaze, Fabien C$$b97 000153599 7001_ $$aLi, Chang$$b98 000153599 7001_ $$aLi, Xiaobo$$b99 000153599 7001_ $$aLi, Xinyue$$b100 000153599 7001_ $$aLiu, Xingmin$$b101 000153599 7001_ $$aMarin, Maximillian G$$b102 000153599 7001_ $$aMarkowski, Julia$$b103 000153599 7001_ $$aNandi, Tannistha$$b104 000153599 7001_ $$aNielsen, Morten M$$b105 000153599 7001_ $$aOjesina, Akinyemi I$$b106 000153599 7001_ $$aPan-Hammarström, Qiang$$b107 000153599 7001_ $$aPark, Peter J$$b108 000153599 7001_ $$aPedamallu, Chandra Sekhar$$b109 000153599 7001_ $$aPedersen, Jakob S$$b110 000153599 7001_ $$aSiebert, Reiner$$b111 000153599 7001_ $$aSu, Hong$$b112 000153599 7001_ $$aTan, 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