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Genome Res DOI:10.1101/gr.163659.113

Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing.

Publication TypeJournal Article
Year of Publication2014
AuthorsHelman, E, Lawrence, MS, Stewart, C, Sougnez, C, Getz, G, Meyerson, M
JournalGenome Res
Date Published2014 Jul
KeywordsBase Sequence, Computational Biology, Databases, Nucleic Acid, DNA Transposable Elements, Exome, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Mutagenesis, Insertional, Neoplasms, Retroelements, Sequence Analysis, DNA

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.


Alternate JournalGenome Res.
PubMed ID24823667
PubMed Central IDPMC4079962
Grant ListU24 CA126546 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24CA126546 / CA / NCI NIH HHS / United States
U24CA143867 / CA / NCI NIH HHS / United States