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Molecular Study Sheds Light on Colorectal Adenomas

By: Joseph Fanelli
Posted: Wednesday, March 28, 2018

As part of a study published in Scientific Reports, scientists identified molecular features of colorectal polyps that may hint at a lesion’s propensity to become cancerous. Lead author Brooke R. Druliner, PhD, of the Mayo Clinic, and colleagues ultimately identified a panel of 124 genes that have alterations between cancer-adjacent polyps and cancer-free polyps in at least 2 platforms.

“The fact that the polyps associated with cancer compared with those that remain benign exhibit genetic mutations that are within cancer pathways and contain mutations in strong cancer driver genes points to the strong necessity for molecular testing upon polyp removal at colonoscopy,” concluded Dr. Druliner and colleagues.

Researchers performed whole-genome sequencing, RNA-sequencing, and reduced representation bisulfite sequencing on over 90 tissues from 31 patients with cancer-adjacent and cancer-free polyps. The cancer-free polyps had polyp tissues matched to their cancer-adjacent counterparts based on polyp size, histology, and dysplasia.

The analysis showed that cancer-adjacent polyps had more mutations, altered expression, and hypermethylation than their cancer-free counterparts. Both groups displayed significant mutations of APC, but mutations in TP53, FBXW7, PIK3CA, KIAA1804, and SMAD2 were only found in cancer-adjacent polyps. Those genes plus SMAD4 were exclusively mutated in cancer-adjacent samples as well. Researchers also observed significant expression changes in GREM1, IGF2, CTGF, and PLAU and both expression and methylation alterations in FES and HES1. Additionally, aberrations found in ERBB3 and E2F8 were specific to cancer-adjacent polyps across all platforms.



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