The detection of RET mutations is a promising test that can diagnose the siblings and offspring of patients with medullary thyroid carcinoma (MTC) before they show any symptoms, according to a new study published in the Journal of Thyroid Research. Prophylactic thyroidectomy can then be considered in these patients.
“Thus, according to the [American Thyroid Association] recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC,” the authors wrote.
Most cases of MTC occur sporadically without a known cause. However, some cases have a genetic component and mutations in the RET gene are associated with the disease. There are 6 hotspot exons in the RET gene where mutations occur most often.
Read more about MTC etiology
A team of researchers led by Mohsen Ghadami, PhD, examined all 6 hot spot exons in the RET gene in 45 Iranian patients from 7 unrelated kindred and 38 apparently sporadic MTC cases. This was to identify germline mutation in the RET gene and their first-degree relatives so that those at risk can undergo prophylactic thyroidectomy.
The researchers also genotyped the first-degree relatives of RET-positive patients.
They found that 17 out of the 45 patients (37.5%) had 8 different germline RET mutations. These were p.C634R, p.M918T, p.C634Y, p.C634F, p.C611Y, p.C618R, p.C630R, and p.L790F.
There was also 1 uncertain variant called p.V648I. Finally, the researchers identified the novel variant p.H648R in 1 of the apparently sporadic cases.
“Evaluation of RET mutations in hot spot exons resulted in the genetic diagnosis of 37.5% of the Iranian MTC patients,” the researchers wrote. They also said that thanks to their analysis, 22 presymptomatic patients were referred for further evaluation and prophylactic thyroidectomy.
They concluded that RET mutation screening is an essential detection method to identify presymptomatic carriers.
Damavandi E, Vand-Rajabpour F, Javadi-Arjmand M, et al. RET proto-oncogene mutational analysis in 45 Iranian patients affected with medullary thyroid carcinoma: report of a new variant. J Thyroid Res. 2021;72508701. doi:10.1155/2021/7250870