TY  - JOUR
A1  - Ewing, Adam D.
A1  - Gacita, Anthony
A1  - Wood, Laura D.
A1  - Ma, Florence
A1  - Xing, Dongmei
A1  - Kim, Min-Sik
A1  - Manda, Srikanth S.
A1  - Abril, Gabriela
A1  - Pereira, Gavin
A1  - Makohon-Moore, Alvin
A1  - Looijenga, Leendert H.J.
A1  - Gillis, Ad J.M.
A1  - Hruban, Ralph H.
A1  - Anders, Robert A.
A1  - Romans, Katharine E.
A1  - Pandey, Akhilesh
A1  - Iacobuzio-Donahue, Christine A.
A1  - Vogelstein, Bert
A1  - Kinzler, Kenneth W.
A1  - Kazazian, Haig H.
A1  - Solyom, Szilvia
T1  - Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution
Y1  - 2015/10/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1536 
EP  - 1545 
DO  - 10.1101/gr.196238.115 
VL  - 25 
IS  - 10 
UR  - http://genome.cshlp.org/content/25/10/1536.abstract 
N2  - 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. 
ER  -