Extremely aggressive course in a poorly differentiated thyroid carcinoma presenting a double mutation of the TERT promoter

Abstract

BRAF and TERT oncogenes hotspot mutations are associated with a more aggressive outcome in thyroid carcinomas (TC). TERT promoter (pTERT) mutations (C228T and C250T) are related to cancer growth and reduced overall- and disease-free survivals in TC. We report a patient followed up for 8 years with a poorly differentiated thyroid carcinoma (PDTC) presenting an extremely aggressive course, who developed a large volume of metastases in a short period. Molecular analysis of the primary tumor revealed two pTERT mutations (C228T and C250T), and no BRAF V600E mutation. pTERT mutations C228T and C250T have been described as mutually exclusive, indicating that one mutation is enough for telomerase activation and exerts its action in thyroid tumorigenesis. This report describes both pTERT hotspot mutations in the same PDTC patient presenting a very aggressive course, even for PDTC, suggesting a relationship between the two events. However, more studies are needed to prove this causality.

Keywords: Molecular marker; Poorly differentiated thyroid carcinoma; TERT promoter mutation.