Somatic transposable element insertions were identified from tumor genome sequences.

  • Major finding: Somatic transposable element insertions were identified from tumor genome sequences.

  • Concept: Insertions are specific to epithelial cancers and tend to occur in mutated or dysregulated genes.

  • Impact: Mutagenic retrotransposition events may be a widespread oncogenic mechanism.

Transposable elements are mobile segments of DNA that are abundant in the genome and contribute to genomic variation among individuals. Transposable element insertions can be mutagenic, but the extent to which somatic insertions contribute to cancer remains unclear, given the difficulties in discerning where transposable elements with nearly identical sequences occur in the genome. Lee and colleagues devised a computational approach to analyze transposable elements in paired-end whole-genome sequencing data from tumor and matched normal blood samples from 43 patients with colorectal, prostate, or ovarian cancer, multiple myeloma, or glioblastoma. Briefly, each read was mapped to both a reference genome and a custom list of known transposable element sequences to identify the exact insertion site, and the mechanism of insertion was inferred from the length and type of inserted sequence. This analysis identified 194 high-confidence retrotransposition events, including 183 long interspersed element-1 insertions, 10 Alu element insertions, and 1 endogenous retrovirus (ERV) element insertion. Interestingly, other than the ERV insertion in a multiple myeloma sample, no high-confidence insertions were identified in blood or brain cancers. Of the identified somatic insertions, one third were located within the untranslated regions or introns of annotated genes, including many implicated in tumor suppression. The target genes were enriched for genes frequently mutated in cancer, and genes with somatic transposable element insertions in tumor samples typically had lower expression than those in matched normal blood. Somatic retrotransposition events were also biased toward hypomethylated regions, providing evidence for a link between tumor-specific genome-wide hypomethylation and transposable element mobilization. Although more studies of the functional impact of these insertion events are needed, these findings suggest that somatic retrotransposition may be common and could confer a selective advantage in certain tumor types.

Lee E, Iskow R, Yang L, Gokcumen O, Haseley P, Luquette LJ, et al. Landscape of somatic retrotransposition in human cancers. Science 2012 Jun 28 [Epub ahead of print].

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