Journal
GENOME RESEARCH
Volume 25, Issue 10, Pages 1536-1545Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.196238.115
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Funding
- National Institutes of Health [1R01GM099875, 1P50GM107632, P50 CA62924]
- Sol Goldman Pancreatic Cancer Research Foundation
- Johns Hopkins GI Core Center
- AACR Basic Cancer Research Fellowship [13-40-01-SOLY]
- Mater Foundation
- NIH [F31CA180682, CA140599, CA179991, RO1-CA43460, RO1-CA57345]
- Virginia and D.K. Ludwig Fund for Cancer Research
- Lustgarten Foundation for Pancreatic Cancer Research
- Sol Goldman Center for Pancreatic Cancer Research
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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 (GO 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.
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