Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
Top Cited Papers
Open Access
- 5 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 52 (3), 306-319
- https://doi.org/10.1038/s41588-019-0562-0
Abstract
About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.Keywords
This publication has 57 references indexed in Scilit:
- Immune signatures correlate with L1 retrotransposition in gastrointestinal cancersGenome Research, 2018
- Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic leukaemiaNature, 2014
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- Comprehensive genomic characterization of squamous cell lung cancersNature, 2012
- LINE-1 Retrotransposition Activity in Human GenomesCell, 2010
- The landscape of somatic copy-number alteration across human cancersNature, 2010
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Mobile Elements: Drivers of Genome EvolutionScience, 2004
- Hot L1s account for the bulk of retrotransposition in the human populationProceedings of the National Academy of Sciences of the United States of America, 2003
- A new retrotransposable human L1 element from the LRE2 locus on chromosome 1q produces a chimaeric insertionNature Genetics, 1994