GSE136629
Hi-ChIP dataset for epigenomics landscape of colorectal cancer
Enhancer aberrations are beginning to emerge as a key feature of colorectal cancers, however, we have limited understanding of epigenomic patterns that distinguish tumors and underlying heterogeneity between tumors. Here, using epigenomic profiling of colorectal tumors, adenomas and normal colon tissues, we identify unique pattern of regulatory elements in colorectal cancer, which could reliably distinguish tumors from normal colon specimens. We define shared and unique enhancer elements during colorectal cancer progression using normal adjacent colon, adenomas and adenocarcinomas. We validate the functional nature of tumor-specific enhancers for important oncogenes such as ASCL2 and Fzd10. NMF clustering identified 4 epigenetic (EPIC) subtypes in colorectal cancer, which mimics consensus molecular subtypes (CMS)1, with an advantage of introducing a novel epigenetically-identifiable subtype with poor prognosis and survival. Based on this correlation, we defined and validated a combination therapeutic strategy of enhancer-blocking BETi with pathway specific inhibitor for 3 CMS subtypes. In conclusion, by comprehensive characterization of chromatin state patterns in colorectal tumors, we define epigenomic patterns during tumor evolution, heterogeneity of enhancers among patients and a combination therapy strategy for CMS-subgroups. Overall design: H3K27Ac HiChIP data for four colorectal cancer cell lines were generated with deep sequencing using the HiSeq4000 sequencer.