Naslov
Association of TERT gene promoter methylation with the aggressiveness of differentiated thyroid cancer

Autori
Periša, Josipa ; Šamija, Ivan ; Blažeković, Ivan ; Romić, Matija ; Raos, Dora ; Sinčić, Nino ; Jukić, Tomislav ; Fröbe, Ana ; Kusić, Zvonko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EACR 2023 Congress Abstracts / - , 2023, 315-315

Skup
EACR2023 - Annual Congress of the European Association for Cancer Research

Mjesto i datum
Torino, Italija, 12.06.2023. - 15.06.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
TERT promotor, methylation, thyroid cancer

Sažetak
Introduction Differentiated thyroid cancer (DTC) incidence has been increasing over decades and accounts for 1-2% of all cancers diagnosed. Overdiagnosis of relatively indolent DTC represents a financial burden to healthcare systems. New biomarkers of aggressiveness are being examined, amongst which molecular markers show promising potential. BRAF V600E mutations, RAS, and TERT promoter mutations (TPMs) are the most common genetic alterations in DTC. However, not all thyroid carcinomas with increased TERT expression harbored TPMs. The methylation of TERT promoter mutation is one of the less studied mechanisms that regulates TERT expression on an epigenetic level. This study aimed to examine the association of TERT gene promoter methylation in differentiated thyroid cancer tissue with metastatic status as a direct measure of the aggressiveness of the disease. Material and Methods This study included 166 patients (78 presented without metastatic disease, 64 with locoregional, and 24 with distant metastases). The region of interest upstream of the transcription start site was selected according to the literature and span over 5 CpGs representative for promoter methylation. DNA was isolated from formalinfixed paraffin-embedded tissue of primary thyroid cancer. Bisulfite conversion, purification, and amplification preceded the pyrosequencing of the selected region. Average methylation of all 5 CpG sites was noted. Association of methylation and metastatic status was examined using the Kruskal-Wallis test (p-value < 0.05 was considered statistically significant). Research was funded by the Croatian Science Foundation project IP- 2019-04-1130. Results and Discussions TERT promoter methylation medians and interquartile ranges (IQR) were 17 % (IQR 6% - 34%) for patients with non-metastatic disease, 23 % (IQR 7, 5% - 33, 5%) and for patients with locoregional metastases and 33% (IQR 24, 5% - 43%) for patients with distant metastatic disease. Methylation of TERT promoter in distant metastatic group was higher and differed significantly from other two groups (P = 0.045, Kruskal-Wallis test, post-hoc analysis Conover). Conclusion In this study we confirmed association of TERT promoter methylation in primary cancer tissue with metastatic status of the disease indicating association of promoter methylation with aggressiveness of differentiated thyroid cancer.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA