BRAF inhibitor treatment of melanoma causing colonic polyps: An alternative hypothesis

Figure 1 Treatment with BRAF inhibitors may lead to colonic adenomas mimicking serrated adenomas with characteristics of cellular senescence, CpG island methylation phenotype, but with BRAF mutations instead substituted by altered RAF homo and hetero dimers. Later selective gene silencing can cause loss of senescence and progression to colorectal cancer. CIMP: CpG island methylation phenotype.

Figure 2 Murine Braf^V637E progression model of intestinal tumorigenesis via the alternative/serrated pathway illustrates the cumulative acquisition of molecular pathway derangement. Intensification of MAP kinase signaling and selective inactivation of genes that govern cellular senescence with progression is a pertinent inference. This figure is based on the model developed by Rad et al[40].