Details

Autor(en) / Beteiligte

• 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
• Veer, Laura Van't
• Caldas, Carlos
• Desmedt, Christine
• Sotiriou, Christos
• Aparicio, Sam
• Foekens, John A
• Eyfjörd, Jórunn Erla
• Lakhani, Sunil R
• Thomas, Gilles
• Myklebost, Ola
• Span, Paul N
• Børresen-Dale, Anne-Lise
• Richardson, Andrea L
• Van de Vijver, Marc
• Vincent-Salomon, Anne
• Van den Eynden, Gert G
• Flanagan, Adrienne M
• Futreal, P Andrew
• Janes, Sam M
• Bova, G Steven
• Stratton, Michael R
• McDermott, Ultan
• Campbell, Peter J

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2014-08, Vol.345 (6196), p.1251343

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.