RET proto-oncogene mutations in thyroid carcinomas: Clinical relevance

Different forms of RET mutations are found in papillary and medullary thyro id carcinomas. Rearrangements with other genes (RET/PTC oncogene) play a ca usative role in a significant proportion of papillary thyroid carcinomas. I n this case, several factors influence the frequency and the type of RET/PT C, such as exposure to radiation, age and histological variant of the papil lary tumor. On the other hand, the presence of the mutation does not seem t o influence the biological behavior of the tumor or its response to convent ional treatment modalities. In the setting of medullary thyroid cancer, ger mline RET pointmutations are implicated in the pathogenesis of virtually al l hereditary forms and somatic pointmutations in nearly half of the sporadi c forms. The clinical impact of this finding is that family members at-risk of hereditary MTC may be screened by genetic analysis, to distinguish thos e 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 RE T gene mutations in thyroid cancer patients. (C) 2000, Editrice Kurtis.