| Literature DB >> 32024998 |
Eva G Alvarez1,2,3, Adrian Baez-Ortega4, Jorge Zamora1,2, Fran Supek5,6, Bernardo Rodriguez-Martin1,2,3, Jonas Demeulemeester7,8, Martin Santamarina1,2,3, Young Seok Ju9,10, Javier Temes1, Daniel Garcia-Souto1, Harald Detering3,11,12, Yilong Li10, Jorge Rodriguez-Castro1, Ana Dueso-Barroso13,14, Alicia L Bruzos1,2,3, Stefan C Dentro7,15,16, Miguel G Blanco17,18, Gianmarco Contino19, Daniel Ardeljan20, Marta Tojo11, Nicola D Roberts10, Sonia Zumalave1,2, Paul A W Edwards21,22, Joachim Weischenfeldt23,24,25, Montserrat Puiggròs13, Zechen Chong26,27, Ken Chen26, Eunjung Alice Lee28,29, Jeremiah A Wala29,30,31, Keiran Raine10, Adam Butler10, Sebastian M Waszak25, Fabio C P Navarro32,33,34, Steven E Schumacher29,30,31, Jean Monlong35, Francesco Maura10,36,37, Niccolo Bolli36,37, Guillaume Bourque35, Mark Gerstein32,33, Peter J Park38, David C Wedge10,16,39, Rameen Beroukhim29,30,31, David Torrents6,13, Jan O Korbel25, Inigo Martincorena10, Rebecca C Fitzgerald19, Peter Van Loo7,8, Haig H Kazazian20, Kathleen H Burns20,40, Peter J Campbell41,42, Jose M C Tubio43,44,45,46.
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.Entities:
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Year: 2020 PMID： 32024998 PMCID： PMC7058536 DOI： 10.1038/s41588-019-0562-0
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330