Science 24 August 2012: 967-971.
Published online 28 June 2012
- Received for publication 19 March 2012.
- Accepted for publication 15 June 2012.
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Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis.
- Frequency of high-confidence somatic L1 insertions varies across 5 colorectal, 7 prostate, 8 ovarian, 7 multiple myeloma, and 16 glioblastoma tumors. Three epithelial cancers (colorectal, prostate, and ovarian) show frequent somatic L1 insertions, whereas no insertions are observed in the blood and brain cancers. One colorectal tumor (CR3518) contains 102 L1 insertions, increasing the average somatic event frequency for colorectal tumors from 9 to 28 when this sample is included.