TY - JOUR A1 - Hashimoto, Kosuke A1 - Suzuki, Ana Maria A1 - Dos Santos, Alexandre A1 - Desterke, Christophe A1 - Collino, Agnese A1 - Ghisletti, Serena A1 - Braun, Emilie A1 - Bonetti, Alessandro A1 - Fort, Alexandre A1 - Qin, Xian-Yang A1 - Radaelli, Enrico A1 - Kaczkowski, Bogumil A1 - Forrest, Alistair R.R. A1 - Kojima, Soichi A1 - Samuel, Didier A1 - Natoli, Gioacchino A1 - Buendia, Marie Annick A1 - Faivre, Jamila A1 - Carninci, Piero T1 - CAGE profiling of ncRNAs in hepatocellular carcinoma reveals widespread activation of retroviral LTR promoters in virus-induced tumors Y1 - 2015/12/01 JF - Genome Research JO - Genome Research SP - 1812 EP - 1824 DO - 10.1101/gr.191031.115 VL - 25 IS - 12 UR - http://genome.cshlp.org/content/25/12/1812.abstract N2 - An increasing number of noncoding RNAs (ncRNAs) have been implicated in various human diseases including cancer; however, the ncRNA transcriptome of hepatocellular carcinoma (HCC) is largely unexplored. We used CAGE to map transcription start sites across various types of human and mouse HCCs with emphasis on ncRNAs distant from protein-coding genes. Here, we report that retroviral LTR promoters, expressed in healthy tissues such as testis and placenta but not liver, are widely activated in liver tumors. Despite HCC heterogeneity, a subset of LTR-derived ncRNAs were more than 10-fold up-regulated in the vast majority of samples. HCCs with a high LTR activity mostly had a viral etiology, were less differentiated, and showed higher risk of recurrence. ChIP-seq data show that MYC and MAX are associated with ncRNA deregulation. Globally, CAGE enabled us to build a mammalian promoter map for HCC, which uncovers a new layer of complexity in HCC genomics. ER -