RET proto-oncogene mutations in thyroid carcinomas: clinical relevance.

Different forms of RET mutations are found in papillary and medullary thyroid carcinomas. Rearrangements with other genes (RET/PTC oncogene) play a causative role in a significant proportion of papillary thyroid carcinomas. In this case, several factors influence the frequency and the type of RET/PTC, such as exposure to radiation, age and histological variant of the papillary tumor. On the other hand, the presence of the mutation does not seem to influence the biological behavior of the tumor or its response to conventional treatment modalities. In the setting of medullary thyroid cancer, germline RET point-mutations are implicated in the pathogenesis of virtually all hereditary forms and somatic point-mutations in nearly half of the sporadic forms. The clinical impact of this finding is that family members at-risk of hereditary MTC may be screened by genetic analysis, to distinguish those carrying or not-carrying the mutation. The last can be reassured on their status and relieved from further follow-up. Those with the mutation may be treated at a pre-clinical stage of the disease or even before the disease is started. The present review is focused on the clinical implication of RET gene mutations in thyroid cancer patients.