Genomics and Epigenomics of Medullary Thyroid Carcinoma: From Sporadic Disease to Familial Manifestations

AbstractOur understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition ofRET as a driver of MTC tumorigenesis in familial MTC. We now have insight into the frequency and prognostic significance of specificRET mutations in sporadic MTC. For example, the most commonRET mutation in sporadic MTC is theRET Met918Thr mutation, the same mutation that underlies MEN2B and a poor prognosticator. This mutation is relatively infrequent in medullary thyroid  microcarcinomas but is over-represented in advanced-stage disease.RAS mutations are detected in 70% of sporadic,RET wild-type MTC. Although next-generation and whole-exome sequencing studies have shown that tumors that are wild-type forRET andRAS mutations essentially lack other recurrent mutations, additional pathways and epigenetic alterations have been implicated in MTC tumorigenesis. Increased insight into the clinical course of patients with familial MTC with specificRET mutations has guided treatment recommendations for these patients. Finally, an understanding of the genomics has informed treatment for patients with advanced MTC. In this review, we will examine the genomics and epigenomics of sporadic and familial MTC, along with the prognostic significance of molecular alterations, management of patients with germlineRET mutations, and treatment strategies for MTC patients.

Source: Endocrine Pathology - January 25, 2021 Category: Pathology Source Type: research