Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.
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ICR Authors
Authors
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,
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,
Document Type
Journal Article
Date
2014-08-01
Date Accepted
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.
Citation
Science (New York, N.Y.), 2014, 345 (6196), pp. 1251343 - ?
Source Title
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
ISSN
0036-8075
eISSN
1095-9203
Research Team
Oncogenetics