TY - JOUR TI - eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways AU - Ahmed, Ibrahim AU - Yang, Shen-Hsi AU - Ogden, Samuel AU - Zhang, Wei AU - Li, Yaoyong AU - The OCCAMs consortium AU - Sharrocks, Andrew D A2 - Hahn, William C A2 - White, Richard M A2 - Davidson, Irwin VL - 12 PY - 2023 DA - 2023/02/20 SP - e80840 C1 - eLife 2023;12:e80840 DO - 10.7554/eLife.80840 UR - https://doi.org/10.7554/eLife.80840 AB - Cancer is driven by both genetic and epigenetic changes that impact on gene expression profiles and the resulting tumourigenic phenotype. Enhancers are transcriptional regulatory elements that are key to our understanding of how this rewiring of gene expression is achieved in cancer cells. Here, we have harnessed the power of RNA-seq data from hundreds of patients with oesophageal adenocarcinoma (OAC) or its precursor state Barrett’s oesophagus coupled with open chromatin maps to identify potential enhancer RNAs and their associated enhancer regions in this cancer. We identify ~1000 OAC-specific enhancers and use these data to uncover new cellular pathways that are operational in OAC. Among these are enhancers for JUP, MYBL2, and CCNE1, and we show that their activity is required for cancer cell viability. We also demonstrate the clinical utility of our dataset for identifying disease stage and patient prognosis. Our data therefore identify an important set of regulatory elements that enhance our molecular understanding of OAC and point to potential new therapeutic directions. KW - oesophageal adenocarcinoma KW - enhancer KW - chromatin KW - eRNA JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -