Using new NGS platforms for analysis, human tumor specimens were used to discover RET mutations in other cancers such as breast carcinoma (RET C634R), endometrial and Merkel-cell carcinomas (RET E511K) and RET V804M in CRC and hepatoma.273 RET C634R is a gain of function mutation, resulting in an autophosphorylation of RET,274 RET 3511K, a gain of function mutation, increased RET and ERK phosphorylation.275 Another gain of function mutation in RET, V804M increased the kinase activity and is considered a gatekeeper due to lack of response to inhibitors like cabozantinib in thyroid cancer.276. The gene discussed is RET; the disease is colorectal carcinoma.