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

Telomerase reverse transcriptase () promoter mutations have been linked to adverse clinical parameters in thyroid cancer, but -expressing tumours are not always mutated. Little is known regarding other -related genetic aberrations. To delineate the role of gene 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 for expression, promoter mutations, promoter hypermethylation and gene copy number (CN) alterations and the results were compared to clinical parameters. Cases with mutation, detectable mRNA expression, CN gain or hypermethylation were classified as aberrant, 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 these gene aberrancies. Moreover, 24 out of 28 FTCs (86%) with expression displayed an evident gene aberration, and statistics showed an increased risk for relapse in FTCs with expression, CN gain or hypermethylation. We conclude that expression in follicular thyroid tumours is coupled to promoter mutations, CN gain and increased promoter methylation. The molecular similarities regarding aberrations between the FTC and FT-UMP groups indicate that a significant subset of FT-UMP cases may display future recurrences. aberrancies are thus promising as future additional markers for determining malignant potential of follicular thyroid tumours.