期刊
NATURE GENETICS
卷 52, 期 3, 页码 306-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41588-019-0562-0
关键词
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资金
- European Research Council (ERC) [716290]
- Ramon y Cajal grant [RYC-2014-14999]
- Spanish Ministry of Economy, Industry and Competitiveness (MINECO) grant [SAF2015-66368-P]
- Xunta de Galicia (Spain) [ED481A-2016/151, ED481A-2017/299, ED481A-2017/306, ED481A-2018/199]
- ERC [757700]
- MINECO [BFU2017-89833-P, BES-2016-078166, SAF2015-73916-JIN]
- MINECO Severo Ochoa award
- CERCA Programme of the Catalan Government
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI16C2387]
- National Institutes of Health [U24CA210978, R01CA188228]
- AEI
- Xunta de Galicia
- FEDER [BFU2013-41554-P, BFU2016-78121-P, ED431F 2016/019]
- My First AIRC grant from the Associazione Italiana Ricerca sul Cancro [17658]
- European Union [703594-DECODE]
- NIH [R01 CA172652, U41 HG007497]
- American Heart Association Institutional Data Fellowship Award [17IF33890015]
- Cancer Research UK [C57387/A21777]
- A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS)
- S.I.E.S. (Societa Italiana di Ematologia Sperimentale)
- SNSF Early Postdoc Mobility fellowship [P2ELP3_155365]
- EMBO Long-Term Fellowship [ALTF 755-2014]
- Danish Medical Research Council [DFF-4183-00233]
- Li Ka Shing foundation
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
- ERC
- Francis Crick Institute from Cancer Research UK [FC001202]
- UK Medical Research Council [FC001202]
- Wellcome Trust [FC001202]
- National Institute of General Medical Sciences [P50GM107632, 1R01GM099875]
- TransTumVar project [PN013600]
- Wellcome Trust grant [09805]
- [K01AG051791]
- [R01CA163705]
- [R01GM124531]
- European Research Council (ERC) [716290] Funding Source: European Research Council (ERC)
- Swiss National Science Foundation (SNF) [P2ELP3_155365] Funding Source: Swiss National Science Foundation (SNF)
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. An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.
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