TY  - JOUR
AU  - Li, Yilong
AU  - Roberts, Nicola D
AU  - Wala, Jeremiah A
AU  - Shapira, Ofer
AU  - Schumacher, Steven E
AU  - Kumar, Kiran
AU  - Khurana, Ekta
AU  - Waszak, Sebastian
AU  - Korbel, Jan O
AU  - Haber, James E
AU  - Imielinski, Marcin
AU  - PCAWGStructuralVariationWorkingGroup
AU  - Weischenfeldt, Joachim
AU  - Beroukhim, Rameen
AU  - Campbell, Peter J
AU  - PCAWGConsortium
TI  - Patterns of somatic structural variation in human cancer genomes.
JO  - Nature 
VL  - 578
IS  - 7793
SN  - 1476-4687
CY  - London [u.a.]
PB  - Nature Publ. Group52462
M1  - DKFZ-2020-02053
SP  - 112 - 121
PY  - 2020
N1  - siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium: https://inrepo02.dkfz.de/record/265691   /   https://doi.org/10.1038/s41586-022-05597-x
AB  - 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.
KW  - Gene Rearrangement: genetics
KW  - Genetic Variation
KW  - Genome, Human: genetics
KW  - Genomics
KW  - Humans
KW  - Mutagenesis, Insertional
KW  - Neoplasms: genetics
KW  - Telomerase: genetics
KW  - TERT protein, human (NLM Chemicals)
KW  - Telomerase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32025012
C2  - pmc:PMC7025897
DO  - DOI:10.1038/s41586-019-1913-9
UR  - https://inrepo02.dkfz.de/record/163800
ER  -