Rusinek Dagmara, Pfeifer Aleksandra, Cieslicka Marta, Kowalska Malgorzata, Pawlaczek Agnieszka, Krajewska Jolanta, Szpak-Ulczok Sylwia, Tyszkiewicz Tomasz, Halczok Monika, Czarniecka Agnieszka, Zembala-Nozynska Ewa, Chekan Mykola, Lamch Roman, Handkiewicz-Junak Daria, Ledwon Aleksandra, Paliczka-Cieslik Ewa, Kropinska Aleksandra, Jarzab Barbara, Oczko-Wojciechowska Malgorzata
Department of Genetic and Molecular Diagnostics of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-102 Gliwice, Poland.
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, 44-102 Gliwice, Poland.
Cancers (Basel). 2020 Jun 17;12(6):1597. doi: 10.3390/cancers12061597.
Telomerase reverse transcriptase promoter (p) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of p mutations in PTC was the aim of our study.
The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. V600E, and p mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(-) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis.
Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(-) PTCs. Deregulation of pathways involved in key cell processes was observed.
p mutations are related to higher PTC aggressiveness. gene was validated as associated with p mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.
端粒酶逆转录酶启动子（p）突变与包括甲状腺乳头状癌（PTC）在内的多种恶性肿瘤的预后较差有关。由于导致TERTp（+）患者预后较差的机制仍不清楚，本研究的目的是寻找PTC中p突变的分子后果。
研究队列包括54例PTC，其中24例有远处转移。对所有病例评估V600E和p突变状态。使用微阵列检测TERTp（+）和TERTp（-）PTC之间基因表达谱的差异。信号通路和基因本体的评估基于基因集富集分析。
59%（32/54）的分析PTC至少有一个突变呈阳性：27例为BRAF（+），其中8例为TERTp（+），1例为NRAS（+），而其他5个样本存在突变。BRAF（+）TERTp（+）和BRAF（+）TERTp（-）PTC中四个基因的表达有显著差异。观察到关键细胞过程中涉及的通路失调。
p突变与PTC的侵袭性较高有关。基因被证实与p突变相关。然而，其在PTC患者诊断或风险分层中的潜在应用需要进一步研究。
