For example, the strongly activating BRAF p.V600E driver commonly present in melanoma, thyroid, ovarian and colorectal cancer has never been identified in a CFC individual (Champion et al., 2011; Rodriguez-Viciana et al., 2006), and KRAS mutations identified in a RASopathy individual are novel hypermorphs and not in the classic mutational hotspots associated with cancer (Schubbert et al., 2007). This evidence concerns the gene BRAF and melanoma.