Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

Adam D. Ewing, Anthony Gacita, Laura D. Wood, Florence Ma, Dongmei Xing, Min Sik Kim, Srikanth S. Manda, Gabriela Abril, Gavin Pereira, Alvin Makohon-Moore, Leendert H.J. Looijenga, Ad J.M. Gillis, Ralph H. Hruban, Robert A. Anders, Katharine E. Romans, Akhilesh Pandey, Christine A. Iacobuzio-Donahue, Bert Vogelstein, Kenneth W. Kinzler, Haig H. KazazianSzilvia Solyom

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth.

Original languageEnglish (US)
Pages (from-to)1536-1545
Number of pages10
JournalGenome Research
Volume25
Issue number10
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution'. Together they form a unique fingerprint.

  • Cite this

    Ewing, A. D., Gacita, A., Wood, L. D., Ma, F., Xing, D., Kim, M. S., Manda, S. S., Abril, G., Pereira, G., Makohon-Moore, A., Looijenga, L. H. J., Gillis, A. J. M., Hruban, R. H., Anders, R. A., Romans, K. E., Pandey, A., Iacobuzio-Donahue, C. A., Vogelstein, B., Kinzler, K. W., ... Solyom, S. (2015). Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution. Genome Research, 25(10), 1536-1545. https://doi.org/10.1101/gr.196238.115