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Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

ABSTRACT: Somatic L1 retrotransposition events have been shown to occur in epithelial cancers1-8. 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. Here we show Human SNP 6.0 Array experiments on DNAs from four colorectal cancer patients (1BV, 2BV, 3BV, and 4BV) with polyps and metastases. Here we characterize the samples for CNVs and compare the samples' CNV status to their respective somatic L1 retrotransposition profile.

ORGANISM(S): Homo sapiens  

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

PROVIDER: E-GEOD-63601 | ArrayExpress | 2015-08-19



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