TERT aberrancies: a screening tool for malignancy in follicular thyroid tumours

Abstract

Telomerase reverse transcriptase (TERT) promoter mutations have been linked to adverse clinical parameters in thyroid cancer, butTERT-expressing tumours are not always mutated. Little is known regarding otherTERT-related genetic aberrations. To delineate the role ofTERTgene aberrancies in follicular thyroid tumours, 95 follicular carcinomas (FTCs), 43 follicular adenomas (FTAs) and 33 follicular tumours of uncertain malignant potential (FT-UMPs) were collected. The tumours were assayed forTERTexpression,TERTpromoter mutations,TERTpromoter hypermethylation andTERTgene copy number (CN) alterations and the results were compared to clinical parameters. Cases with mutation, detectable mRNA expression, CN gain or hypermethylation were classified asTERTaberrant, and these aberrancies were regularly found in FTC and FT-UMP but uncommonly found in FTA. In total, 59% FTCs and 63% FT-UMPs exhibited one or more of theseTERTgene aberrancies. Moreover, 24 out of 28 FTCs (86%) withTERTexpression displayed an evidentTERTgene aberration, and statistics showed an increased risk for relapse in FTCs withTERTexpression, CN gain or hypermethylation. We conclude thatTERTexpression in follicular thyroid tumours is coupled to promoter mutations, CN gain and increased promoter methylation. The molecular similarities regardingTERTaberrations between the FTC and FT-UMP groups indicate that a significant subset of FT-UMP cases may display future recurrences.TERTaberrancies are thus promising as future additional markers for determining malignant potential of follicular thyroid tumours.