Endocrine Abstracts

In this study we describe a new allelic variant of RET, identified in a family with Medullary Thyroid Cancer (MTC) and negative for the classical RET mutations, that causes an Arg982Cys substitution in exon 18.

The “in silico” analysis has shown that this variant has a reduced compatibility [score 15] with the normal biological activity of the native protein and could therefore be a transforming mutation.

The aim of this work was to verify whether this new variant was correlated to MTC development.

The study was conducted on 6 family members, 2 affected with MTC and 4 healthy subjects, and on 172 patients with sporadic MTC. We also studied 176 healthy controls. The new RET variant was analized by direct sequencing of PCR amplified DNA.

Our data showed the presence of the Arg982Cys variant in 3 subjects of the family, including 2 healthy subjects and 1 patient with MTC. In the group of sporadic MTC tumors the Arg982Cys variant was observed in 12/172 (6.9%) cases. The allelic frequency of Arg982Cys was 3.5% (12/344). Among the 176 control subjects, 10 (5.7%) had the Arg982Cys variant and the allelic frequency was 2.8% (10/352). Comparing the allelic frequency of the Arg982Cys variant in the two groups [MTC vs. healthy subjects] no statistically significant difference was observed.

In conclusion, this study describes a new variant of RET that does not seem to be predisposing to the development of MTC but may instead be considered a true polymorphism, never described up to now. The ”in silico” analysis identifies an altered biological activity of the mutant protein that could still play a pathogenic role in other diseases. It should be noted that this variant has been described in some cases associated with Undine’s syndrome, which was not observed in our subjects.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector