Journal
SCIENCE
Volume 345, Issue 6196, Pages 531-531Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1251343
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Funding
- Marie Curie Fellowship [328264]
- Wellcome Trust [WT100183MA]
- Chordoma Foundation
- Skeletal Cancer Action Trust
- European Molecular Biology Organization [LTF 1203-2012, 1287-2012]
- CRUK Clinician Scientist fellowship
- National Institute for Health Research
- University College London Hospitals Biomedical Research Centre
- Cancer Research UK University College London Experimental Cancer Centre
- Brussels Region-Impulse Programme Life Sciences
- European Union (BASIS)
- Wellcome Trust
- CRUK [C5047/A14835]
- Dallaglio Foundation
- Bob Champion Trust
- Orchid Cancer appeal
- RoseTrees Trust
- North West Cancer Research Fund, Big C
- Grand Charity of Freemasons
- Research Foundation Flanders (FWO)
- 14M Genomics Limited
- BBSRC [BBS/E/F/00042686, BBS/E/F/00044431] Funding Source: UKRI
- MRC [G0900871] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/F/00042686, BBS/E/F/00044431] Funding Source: researchfish
- Cancer Research UK [16942, 15007, 14835, 19556, 17528] Funding Source: researchfish
- Medical Research Council [G0900871] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
- Rosetrees Trust [M35-F1-CD1] Funding Source: researchfish
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Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction. Because 3' transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3' transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3' transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3' transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.
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