Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.
Van Loo, P
van't Veer, L
Van de Vijver, M
Van den Eynden, GG
MetadataShow full item record
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.
Version of record
ICGC Breast Cancer Group
ICGC Bone Cancer Group
ICGC Prostate Cancer Group
DNA Transposable Elements
Long Interspersed Nucleotide Elements
License start date
Science (New York, N.Y.), 2014, 345 (6196), pp. 1251343 - ?
Showing items related by title, author, creator and subject.
Plasma Carotenoid- and Retinol-Weighted Multi-SNP Scores and Risk of Breast Cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium Hendrickson, SJ; Lindstroem, S; Eliassen, AH; Rosner, BA; Chen, C; Barrdahl, M; Brinton, L; Buring, J; Canzian, F; Chanock, S; Clavel-Chapelon, F; Figueroa, JD; Gapstur, SM; Garcia-Closas, M; Gaudet, MM; Haiman, CA; Hazra, A; Henderson, B; Hoover, R; Husing, A; Johansson, M; Kaaks, R; Khaw, K-T; Kolonel, LN; Le Marchand, L; Lissowska, J; Lund, E; McCullough, ML; Peplonska, B; Riboli, E; Sacerdote, C; Sanchez, M-J; Tjonneland, A; Trichopoulos, D; van Gils, CH; Yeager, M; Kraft, P; Hunter, DJ; Ziegler, RG; Willett, WC (AMER ASSOC CANCER RESEARCH, 2013-05)Background: Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in beta-carotene ...
Can routine data be used to support cancer clinical trials? A historical baseline on which to build: retrospective linkage of data from the TACT (CRUK 01/001) breast cancer trial and the National Cancer Data Repository. Kilburn, LS; Aresu, M; Banerji, J; Barrett-Lee, P; Ellis, P; Bliss, JM (2017-11-23)BACKGROUND: Randomised clinical trials (RCTs) are the gold standard for evaluating new cancer treatments. They are, however, expensive to conduct, particularly where long-term follow-up of participants is required. Tracking ...
Bridgett, S; Campbell, J; Lord, CJ; Ryan, CJ (2017-07-26)Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ...