期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms14400
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资金
- NIH [P50CA150964, R01 CA160356, R01 CA143237, R01 CA204279, R01 CA193677, R01 CA206505, F30 CA186633, T32 GM007250, TL1 RR02499]
In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin. Many activate known oncogenes, and CRC growth can be mitigated through pharmacologic inhibition or genome editing of these loci. Nearly half of all GWAS CRC risk loci co-localize to recurrently activated enhancers. These findings indicate that the CRC epigenome is defined by highly recurrent epigenetic alterations at enhancers which activate a common, aberrant transcriptional programme critical for CRC growth and survival.
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