| Literature DB >> 25082706 |
Yilong Li1, Young Seok Ju1, Jose M C Tubio1, Inigo Martincorena1, Susanna L Cooke1, Marta Tojo2, Gunes Gundem1, Christodoulos P Pipinikas3, Jorge Zamora1, Keiran Raine1, Andrew Menzies1, Pablo Roman-Garcia1, Anthony Fullam1, Moritz Gerstung1, Adam Shlien1, Patrick S Tarpey1, Elli Papaemmanuil1, Stian Knappskog1,4,5, Peter Van Loo1,6, Manasa Ramakrishna1, Helen R Davies1, John Marshall1, David C Wedge1, Jon W Teague1, Adam P Butler1, Serena Nik-Zainal1,7, Ludmil Alexandrov1, Sam Behjati1, Lucy R Yates1, Niccolo Bolli1,8, Laura Mudie1, Claire Hardy1, Sancha Martin1, Stuart McLaren1, Sarah O'Meara1, Elizabeth Anderson1, Mark Maddison1, Stephen Gamble1, Christopher Foster9, Anne Y Warren7, Hayley Whitaker10, Daniel Brewer11,12, Rosalind Eeles11, Colin Cooper11,12, David Neal10, Andy G Lynch10, Tapio Visakorpi13, William B Isaacs14, Laura Van't Veer15, Carlos Caldas10, Christine Desmedt16, Christos Sotiriou16, Sam Aparicio17, John A Foekens18, Jórunn Erla Eyfjörd19, Sunil R Lakhani20,21,22, Gilles Thomas23, Ola Myklebost24, Paul N Span25, Anne-Lise Børresen-Dale24, Andrea L Richardson26, Marc Van de Vijver27, Anne Vincent-Salomon28,29, Gert G Van den Eynden30, Adrienne M Flanagan31,32, P Andrew Futreal1,33, Sam M Janes3, G Steven Bova13, Michael R Stratton1, Ultan McDermott1, Peter J Campbell1,7,8.
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.Entities:
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Year: 2014 PMID： 25082706 PMCID： PMC4380235 DOI： 10.1126/science.1251343
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728