Germline <i>RET</i> variants in medullary thyroid carcinoma: A single-center experience from 2019 to 2025.

Abstract

e18051 Background: Medullary thyroid carcinoma (MTC) accounts for approximately 1–2% of all thyroid cancers and is hereditary in up to 25% of cases, most commonly due to germline mutations in the RET proto-oncogene. Systematic genetic testing is recommended for all patients diagnosed with MTC to identify hereditary forms and guide familial screening. We report our institutional experience with germline RET testing in patients with MTC over a six-year period. Methods: Between 2019 and 2025, a total of 28 patients diagnosed with MTC were referred for germline genetic testing. The cohort included 22 women and 6 men, with a median age at diagnosis of 40 years. Germline analysis of the RET gene was performed using Sanger sequencing, covering exons 10, 11, 13, 15 and 16. Clinical, pathological, and genetic data were retrospectively reviewed. Results: Pathogenic or likely pathogenic germline RET mutations were identified in 6 of 28 patients (21.4%), including 3 women and 3 men. Notably, all detected mutations were located in exon 11 of the RET gene. Among mutation carriers, 19 had clinical features suggestive of hereditary disease, including [pheochromocytoma / hyperparathyroidism / family history / bilateral disease?], while 9 cases appeared sporadic at presentation. Conclusions: In this single-center cohort, approximately one-fifth of patients with medullary thyroid carcinoma harbored a germline RET mutation, consistent with reported international data. The exclusive involvement of exon 11 in mutation-positive cases highlights its critical role in hereditary MTC and supports systematic germline RET testing in all patients, regardless of clinical presentation. Early identification of mutation carriers enables appropriate familial counseling, targeted surveillance, and personalized management.