Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes

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, Eeles, Rosalind, Cooper, Colin, Neal, David, Lynch, Andy G, Visakorpi, Tapio, Isaacs, William B, van't Veer, Laura, 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

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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
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
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: 01 May 2020 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/50243
DOI: 10.1126/science.1251343

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