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

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Date
2014-08
ICR Author
Eeles, Rosalind
Author
Tubio, JMC
Li, Y
Ju, YS
Martincorena, I
Cooke, SL
Tojo, M
Gundem, G
Pipinikas, CP
Zamora, J
Raine, K
Menzies, A
Roman-Garcia, P
Fullam, A
Gerstung, M
Shlien, A
Tarpey, PS
Papaemmanuil, E
Knappskog, S
Van Loo, P
Ramakrishna, M
Davies, HR
Marshall, J
Wedge, DC
Teague, JW
Butler, AP
Nik-Zainal, S
Alexandrov, L
Behjati, S
Yates, LR
Bolli, N
Mudie, L
Hardy, C
Martin, S
McLaren, S
O'Meara, S
Anderson, E
Maddison, M
Gamble, S
Foster, C
Warren, AY
Whitaker, H
Brewer, D
Eeles, R
Cooper, C
Neal, D
Lynch, AG
Visakorpi, T
Isaacs, WB
Veer, LV
Caldas, C
Desmedt, C
Sotiriou, C
Aparicio, S
Foekens, JA
Eyfjörd, JE
Lakhani, SR
Thomas, G
Myklebost, O
Span, PN
Børresen-Dale, A-L
Richardson, AL
Van de Vijver, M
Vincent-Salomon, A
Van den Eynden, GG
Flanagan, AM
Futreal, PA
Janes, SM
Bova, GS
Stratton, MR
McDermott, U
Campbell, PJ
ICGC Breast Cancer Group
ICGC Bone Cancer Group
ICGC Prostate Cancer Group
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Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/1850
DOI
https://doi.org/10.1126/science.1251343
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
ICGC Breast Cancer Group
ICGC Bone Cancer Group
ICGC Prostate Cancer Group
Chromatin
Humans
Neoplasms
Translocation, Genetic
DNA Transposable Elements
Transduction, Genetic
Mutagenesis, Insertional
Long Interspersed Nucleotide Elements
Genome, Human
Exons
Carcinogenesis
Research team
Oncogenetics
Language
eng
License start date
2014-08
Citation
Science (New York, N.Y.), 2014, 345 (6196), pp. 1251343 - ?

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