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.

Original publication

DOI

10.1126/science.1251343

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

08/2014

Volume

345

Addresses

Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.

Keywords

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