Familial medullary thyroid carcinoma: A rare germline mutation in the RET proto-oncogene

Abstract

Medullary thyroid carcinoma (MTC) is an aggressive thyroid cancer that generally accounts for more than 10% of thyroid malignancies. Approximately 25% of MTC cases exhibit up hereditary traits. Dominantly inherited syndromes of MTC such as multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) are linked to gain-of-function alterations in the RET proto-oncogene. This latter encodes a receptor tyrosine kinase involved in several signal transduction pathways in neural precursor cells. Therefore, genetic screening for RET mutations facilitates early disease diagnosis and the possibility of prophylactic thyroidectomy for at-risk relatives. This study underscores the relevance of RET genetic analysis by describing a familial case of MTC with c.1597G>T (p.Gly533Cys) mutation in the RET gene.