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.
journal_name
Genome Resjournal_title
Genome researchauthors
Ewing AD,Gacita A,Wood LD,Ma F,Xing D,Kim MS,Manda SS,Abril G,Pereira G,Makohon-Moore A,Looijenga LH,Gillis AJ,Hruban RH,Anders RA,Romans KE,Pandey A,Iacobuzio-Donahue CA,Vogelstein B,Kinzler KW,Kazazian HH Jr,Soldoi
10.1101/gr.196238.115subject
Has Abstractpub_date
2015-10-01 00:00:00pages
1536-45issue
10eissn
1088-9051issn
1549-5469pii
gr.196238.115journal_volume
25pub_type
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