E. Shyam P. Reddy: Crypt Density and Epigenetic Changes in Intestinal Tumorigenesis Driven by Apc Mutations
E. Shyam P. Reddy, Professor and Director, Cancer Biology Program, Dept OB/GYN at Morehouse School of Medicine, posted on Linkedin:
“Crypt density and epigenetic changes are important in intestinal tumourigenesis driven by Apc mutations, the most common initiating event in conventional adenomas that activates Wnt signaling. Gaynor and colleagues engineered two mouse models with inducible Apc deletion in intestinal stem cells (ISCs) arising from either self-renewal or dedifferentiation. They found that Apc deletion only drove tumor formation when mutant intestinal crypts were in close proximity, regardless of ISC source.
Additionally, they discovered that thousands of enhancer elements became more accessible in adenoma-resident Apc-null ISCs, activating additional oncogenes. The authors conclude that Apc mutations trigger adenomas only when Wnt-activated crypts reach a “critical mass” accompanied by altered chromatin accessibility at thousands of enhancers. These findings provide new insight into the early steps of intestinal tumor initiation.
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