Characterization of V804M-mutated RET proto-oncogene associated with familial medullary thyroid cancer, report of the largest Turkish family

Purpose Analysis of the RET proto-oncogen is very important for diagnosis and prognosis of medullary thyroid cancer (MTC). Genotype–phenotype correlation is also well known. Here we report features of the largest known family in Turkey with the V804M-mutated RET proto-oncogene. Methods Thirty members from three generations were evaluated. A RET proto-oncogen mutation, calcitonin (Ct) measurement and thyroid ultrasound were performed on all individuals. Seventeen members had V804M mutation. Fourteen of these patients underwent total thyroidectomy and additional central lymph node dissection for five subjects. Results The mean age of patients with MTC was 46.5 (30–61) years. The mean calcitonin level of RET positive members was 13.27 pg/mL (1–49.8 pg/mL). Three had a basal Ct level above normal limits. Seven of the 14 patients were diagnosed with MTC, and two were diagnosed with papillary thyroid cancer without MTC. One patient had central neck metastasis. Hyperparathyroidism or pheochromocytoma was not detected in any case. Patients who were RET negative, had normal Ct levels and no suspected nodule on ultrasound examination. Conclusions Our study revealed a relatively good prognosis in patients with V804M mutation. Despite the surgery was performed in older age no advance disease was observed.