RET Proto-Oncogene Mutations: Impact on Diagnosis, Treatment and Prognosis of MTC

Abstract

Variants of MTC result from different mutations in exons of the RET gene. RET proto-oncogene is activated by a DNA rearrangement and it is one of the first tyrosine kinase receptor (RTK) proteins found to play a role in neoplasia. Early detection using genetic screening has become the gold standard of therapy, followed by prophylactic thyroidectomy. RET-kinase inhibitors have been developed recently for the treatment of MTC and are currently at various phases of pre- and clinical trials. Numerous autosomal dominantly inherited mutations have been demonstrated to activate RET constitutively. These mutations in separate populations are believed to be correlated with a rather heterogeneous prototype across countries. As such, one objective of this study was to demonstrate a geographical pattern of RET mutations in various populations. Advances in RET genetic screening have facilitated for the rapid recognition of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show signs of the disease. In this chapter, we will discuss oncogenic RET signaling, RET inhibitors and the major RET mutations found in MTC and the necessity of RET genetic screening for the early diagnosis of MTC patients, using American Thyroid Association guidelines and genotype-phenotype correlation.