@article{0f1a1ae90ac54330bd6f50e28bccf41e,
title = "Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes",
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",
author = "{AUTHOR GROUP} and Tubio, {Jose M. C.} and Yilong Li and Ju, {Young Seok} and Inigo Martincorena and Cooke, {Susanna L.} and Marta Tojo and Gunes Gundem and Pipinikas, {Christodoulos P.} and Jorge Zamora and Keiran Raine and Andrew Menzies and Pablo Roman-Garcia and Anthony Fullam and Moritz Gerstung and Adam Shlien and Tarpey, {Patrick S.} and Elli Papaemmanuil and Stian Knappskog and {van Loo}, Peter and Manasa Ramakrishna and Davies, {Helen R.} and John Marshall and Wedge, {David C.} and Teague, {Jon W.} and Butler, {Adam P.} and Serena Nik-Zainal and Ludmil Alexandrov and Sam Behjati and Yates, {Lucy R.} and Niccolo Bolli and Laura Mudie and Claire Hardy and Sancha Martin and Stuart McLaren and Sarah O'Meara and Elizabeth Anderson and Mark Maddison and Stephen Gamble and Christopher Foster and Warren, {Anne Y.} and Hayley Whitaker and Daniel Brewer and Rosalind Eeles and Colin Cooper and David Neal and Lynch, {Andy G.} and Tapio Visakorpi and Isaacs, {William B.} and {van de Vijver}, Marc",
year = "2014",
doi = "https://doi.org/10.1126/science.1251343",
language = "English",
volume = "345",
pages = "531--+",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6196",
}