Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing
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Helman-2014-Somatic retrotranspo.pdf
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Author(s)
Helman, Elena
Lawrence, Michael S.
Stewart, Chip
Sougnez, Carrie
Getz, Gad
Meyerson, Matthew L.
Date Issued
May 2014
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory Press
Citation
Helman, E., M. S. Lawrence, C. Stewart, C. Sougnez, G. Getz, and M. Meyerson. “Somatic Retrotransposition in Human Cancer Revealed by Whole-Genome and Exome Sequencing.” Genome Research 24, no. 7 (May 13, 2014): 1053–1063.
Version
Final published version
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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Creative Commons Attribution-Noncommerical
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DOI of Published Version
https://doi.org/10.1101/gr.163659.113
