RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant

Elia Damavandi; Fatemeh Vand-Rajabpour; Maliheh Javadi-Arjmand; Mohammad-Reza Mohajeri Tehrani; Bagher Larijani; Majid Kabuli; Mohsen Ghadami

doi:10.1155/2021/7250870

RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant

J Thyroid Res. 2021 Nov 3:2021:7250870. doi: 10.1155/2021/7250870. eCollection 2021.

Authors

Elia Damavandi^{1

2}, Fatemeh Vand-Rajabpour³, Maliheh Javadi-Arjmand³, Mohammad-Reza Mohajeri Tehrani⁴, Bagher Larijani⁴, Majid Kabuli³, Mohsen Ghadami^{3

4

5}

Affiliations

¹ Specialized Medical Genetic Center (SMGC) of ACECR, Tehran, Iran.
² Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran.
³ Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Cardiac Primary Research Center, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Background: The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14-16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed.

Results: Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients.

Conclusion: RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.