Deprecated: Unparenthesized `a ? b : c ? d : e` is deprecated. Use either `(a ? b : c) ? d : e` or `a ? b : (c ? d : e)` in /home/institu2/public_html/bibliographie/ecrire/inc/utils.php on line 2576
journalArticle Shukla R. Upton K. R. Munoz-Lopez M. Gerhardt D. J. Fisher M. E. Nguyen T. Brennan P. M. Baillie J. K. Collino A. Ghisletti S. Sinha S. Iannelli F. Radaelli E. Dos Santos A. Rapoud D. Guettier C. Samuel D. Natoli G. Carninci P. Ciccarelli F. D. Garcia-Perez J. L. Faivre J. Faulkner G. J. Adult Aged Animals Carcinoma Hepatocellular/ genetics Cell Line Insertional P-Glycoproteins/genetics Repressor Proteins/genetics Tumor Suppressor Proteins/genetics Neoplastic DNA Mutational Analysis Female Genes Tumor Cell Transformation Tumor Suppressor Humans Liver Neoplasms/ genetics Long Interspersed Nucleotide Elements Male Mice Middle Aged Mutagenesis Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma LINE-1 (L1) retrotransposons are mobile genetic elements comprising 17% of the human genome. New L1 insertions can profoundly alter gene function and cause disease, though their significance in cancer remains unclear. Here, we applied enhanced retrotransposon capture sequencing (RC-seq) to 19 hepatocellular carcinoma (HCC) genomes and elucidated two archetypal L1-mediated mechanisms enabling tumorigenesis. In the first example, 4/19 (21.1%) donors presented germline retrotransposition events in the tumor suppressor mutated in colorectal cancers (MCC). MCC expression was ablated in each case, enabling oncogenic beta-catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18 (ST18) was activated by a tumor-specific L1 insertion. Experimental assays confirmed that the L1 interrupted a negative feedback loop by blocking ST18 repression of its enhancer. ST18 was also frequently amplified in HCC nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene. These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in HCC. 101-11 Mar 28 2013 Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma Cell 153 1 ISSN 1097-4172 (ELECTRONIC); 0092-8674 (LINKING)