Our understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition of RET as a driver of MTC tumorigenesis in familial MTC. We now have insight into the frequency and prognostic significance of specific RET mutations in sporadic MTC. For example, the most common RET mutation in sporadic MTC is the RET 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 for RET and RAS 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 specific RET 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 germline RET mutations, and treatment strategies for MTC patients.

自从最初认识到RET是家族性 MTC 中 MTC 肿瘤发生的驱动因素以来，我们对甲状腺髓样癌 (MTC) 的基因组学和表观基因组学的理解已经取得了进展。我们现在可以深入了解散发性 MTC 中特定RET突变的频率和预后意义。例如，散发性 MTC 中最常见的RET突变是RET Met918Thr 突变，与 MEN2B 的基础突变相同，并且预后不佳。这种突变在甲状腺髓样微小癌中相对少见，但在晚期疾病中过多。在 70% 的散发性RET中检测到RAS突变野生型 MTC。尽管下一代和全外显子组测序研究表明，RET和RAS突变的野生型肿瘤基本上没有其他复发突变，但其他途径和表观遗传改变与 MTC 肿瘤发生有关。对具有特定RET突变的家族性 MTC 患者临床病程的深入了解为这些患者提供了治疗建议。最后，对基因组学的了解为晚期 MTC 患者的治疗提供了信息。在这篇综述中，我们将研究散发性和家族性 MTC 的基因组学和表观基因组学，以及分子改变的预后意义，生殖系RET患者的管理MTC 患者的突变和治疗策略。