%0 Journal Article
%A Li, Yilong
%A Roberts, Nicola D
%A Wala, Jeremiah A
%A Shapira, Ofer
%A Schumacher, Steven E
%A Kumar, Kiran
%A Khurana, Ekta
%A Waszak, Sebastian
%A Korbel, Jan O
%A Haber, James E
%A Imielinski, Marcin
%A PCAWGStructuralVariationWorkingGroup
%A Weischenfeldt, Joachim
%A Beroukhim, Rameen
%A Campbell, Peter J
%A PCAWGConsortium
%T Patterns of somatic structural variation in human cancer genomes.
%J Nature 
%V 578
%N 7793
%@ 1476-4687
%C London [u.a.]
%I Nature Publ. Group52462
%M DKFZ-2020-02053
%P 112 - 121
%D 2020
%Z siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium: https://inrepo02.dkfz.de/record/265691   /   https://doi.org/10.1038/s41586-022-05597-x
%X A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
%K Gene Rearrangement: genetics
%K Genetic Variation
%K Genome, Human: genetics
%K Genomics
%K Humans
%K Mutagenesis, Insertional
%K Neoplasms: genetics
%K Telomerase: genetics
%K TERT protein, human (NLM Chemicals)
%K Telomerase (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32025012
%2 pmc:PMC7025897
%R 10.1038/s41586-019-1913-9
%U https://inrepo02.dkfz.de/record/163800