Retrotransposons constitute a major source of genetic variation, and somatic
retrotransposon insertions have been reported in
cancer. Here, we applied TranspoSeq, a computational framework that identifies
retrotransposon insertions from sequencing data, to whole genomes from 200
tumor/normal pairs across 11
tumor types as part of The
Cancer Genome Atlas (TCGA) Pan-
Cancer Project. In addition to novel germline polymorphisms, we find 810 somatic
retrotransposon insertions primarily in lung squamous, head and neck, colorectal, and
endometrial carcinomas. Many somatic
retrotransposon insertions occur in known cancer genes. We find that high somatic retrotransposition rates in
tumors are associated with high rates of genomic rearrangement and somatic mutation. Finally, we developed TranspoSeq-Exome to interrogate an additional 767
tumor samples with hybrid-capture exome data and discovered 35 novel somatic
retrotransposon insertions into exonic regions, including an insertion into an exon of the PTEN tumor suppressor gene. The results of this large-scale, comprehensive analysis of
retrotransposon movement across
tumor types suggest that somatic
retrotransposon insertions may represent an important class of structural variation in
cancer.