Multiple endocrine neoplasia type 2 and the RET protooncogene: From bedside to bench to bedside

Although the initial characterization of the various MEN-2 associated phenotypes (familial medullary thyroid cancer, multiple endocrine neoplasia 2A and 2B) evolved at the bedside, it was at the bench where the underlying RET (REarranged during Transfection) germline mutations were identified. Molecular information has revolutionized our understanding and continues to transform the clinical management of this fascinating endocrine tumor syndrome of neural crest derivation, which consists of medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia/adenoma. DNA-based identification of RET carriers did not require comprehension of the gene, but was a prerequisite for clarifying gene function and devising biologic compounds blocking RET phosphorylation. With the continuing expansion of our knowledge about the underlying molecular mechanisms and our growing therapeutic abilities, multiple endocrine neoplasia type 2 is gradually returning home to the bedside, closing the loop from bedside to bench to bedside.