Study Points to Colorectal Cancer Risk Gene, 'Super Enhancer' Influenced by Inflammation

In Nature Communications, an Icahn School of Medicine at Mount Sinai-led team presents evidence for a super enhancer complex that regulates the apparent colorectal carcinoma driver gene PDZK1IP1 and responds to inflammatory features in the tumor microenvironment. Using chromatin immunoprecipitation sequencing focused on the H3K27ac epigenetic histone modification, the investigators profiled potential super enhancer sequences in fresh tumor and normal samples from 15 colon cancer patients undergoing surgery, focusing in on recurrent super enhancers that respond to inflammatory cytokines and boost PDZK1IP1 gene expression. In contrast, they found that targeting one of the super enhancers with CRISPR-based gene editing could dial down PDZK1IP1 expression and curb xenograft colorectal cancer tumor models in mice. "What this means for most patients with colon cancer is that inflammation that's occurring in the tumor is contributing to the tumor's growth," senior author Ramon Parsons, director of Icahn School of Medicine at Mount Sinai's Tisch Cancer Institute, said in a statement. "This stresses the importance of understanding what we can do to curb the inflammatory effects in the colon through prevention or understanding what dietary effects might have on the microenvironment in the colon."