Eunjung Lee1,2, Rebecca Iskow3, Lixing Yang1, Omer Gokcumen3, Psalm Haseley1,2, Lovelace J. Luquette III1, Jens G. Lohr4,5, Christopher C. Harris6, Li Ding6, Richard K. Wilson6, David A. Wheeler7, Richard A. Gibbs7, Raju Kucherlapati2,8, Charles Lee3, Peter V. Kharchenko1,9,*, Peter J. Park1,2,9,*, The Cancer Genome Atlas Research Network
1Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
2Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA.
3Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
4The Eli and Edythe Broad Institute, Cambridge, MA 02412, USA.
5Dana-Farber Cancer Institute, Boston, MA 02115, USA.
6The Genome Institute, Washington University, School of Medicine, St. Louis, MO 63108, USA.
7Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
8Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
9Informatics Program, Children’s Hospital, Boston, MA 02115, USA.
*To whom correspondence should be addressed. eter V. Kharchenko, Peter J. Park
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.