Tubio, Jose M. C., Li, Yilong, Ju, Young Seok, Martincorena, Inigo, Cooke, Susanna L., Tojo, Marta, Gundem, Gunes, Pipinikas, Christodoulos P., Zamora, Jorge, Raine, Keiran, Menzies, Andrew, Roman-Garcia, Pablo, Fullam, Anthony, Gerstung, Moritz, Shlien, Adam, Tarpey, Patrick S., Papaemmanuil, Elli, Knappskog, Stian, Van Loo, Peter, Ramakrishna, Manasa, Davies, Helen R., Marshall, John, Wedge, David C., Teague, Jon W., Butler, Adam P., Nik-Zainal, Serena, Alexandrov, Ludmil, Behjati, Sam, Yates, Lucy R., Bolli, Niccolo, Mudie, Laura, Hardy, Claire, Martin, Sancha, McLaren, Stuart, O'Meara, Sarah, Anderson, Elizabeth, Maddison, Mark, Gamble, Stephen, Foster, Christopher, Warren, Anne Y., Whitaker, Hayley, Brewer, Daniel ORCID: https://orcid.org/0000-0003-4753-9794, Eeles, Rosalind, Cooper, Colin
ORCID: https://orcid.org/0000-0003-2013-8042, Neal, David, Lynch, Andy G., Visakorpi, Tapio, Isaacs, William B., van't Veer, Laura and Caldas, Carlos
and ICGC Breast Cancer Group
(2014)
Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.
Science, 345 (6196).
ISSN 0036-8075
Abstract
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.
Item Type: | Article |
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Additional Information: | Copyright © 2014, American Association for the Advancement of Science. |
Uncontrolled Keywords: | carcinogenesis,chromatin,dna transposable elements,exons,genome, human,humans,long interspersed nucleotide elements,mutagenesis, insertional,neoplasms,transduction, genetic,translocation, genetic,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
Depositing User: | Pure Connector |
Date Deposited: | 08 Oct 2014 08:48 |
Last Modified: | 03 Nov 2022 15:38 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/50243 |
DOI: | 10.1126/science.1251343 |
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