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Int. J. Mol. Sci. 2018, 19(9), 2647; https://doi.org/10.3390/ijms19092647

Coexistence of TERT Promoter Mutations and the BRAF V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients

1
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland
2
Tumor Pathology Department, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland
3
Department of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland
*
Author to whom correspondence should be addressed.
Received: 27 July 2018 / Revised: 28 August 2018 / Accepted: 30 August 2018 / Published: 6 September 2018
(This article belongs to the Special Issue Cell and Molecular Biology of Thyroid Disorders)
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Abstract

TERT promoter (TERTp) mutations are important factors in papillary thyroid carcinomas (PTCs). They are associated with tumor aggressiveness, recurrence, and disease-specific mortality and their use in risk stratification of PTC patients has been proposed. In this study we investigated the prevalence of TERTp mutations in a cohort of Polish patients with PTCs and the association of these mutations with histopathological factors, particularly in coexistence with the BRAF V600E mutation. A total of 189 consecutive PTC specimens with known BRAF mutational status were evaluated. TERTp mutations were detected in 8.5% of cases (16/189) with the C228T mutation being the most frequent. In six of the PTC specimens (3.2%), four additional TERTp alterations were found, which included one known polymorphism (rs2735943) and three previously unreported alterations. The association analysis revealed that the TERTp hotspot mutations were highly correlated with the presence of the BRAF V600E mutation and their coexistence was significantly associated with gender, advanced patient age, advanced disease stage, presence of lymph node metastases, larger tumor size, and tumor-capsule infiltration. While correlations were identified, the possibility of TERTp mutations being key molecular modulators responsible for PTC aggressiveness requires further studies. View Full-Text
Keywords: TERTp mutation; BRAF V600E; papillary thyroid cancer TERTp mutation; BRAF V600E; papillary thyroid cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Rusinek, D.; Pfeifer, A.; Krajewska, J.; Oczko-Wojciechowska, M.; Handkiewicz-Junak, D.; Pawlaczek, A.; Zebracka-Gala, J.; Kowalska, M.; Cyplinska, R.; Zembala-Nozynska, E.; Chekan, M.; Chmielik, E.; Kropinska, A.; Lamch, R.; Jurecka-Lubieniecka, B.; Jarzab, B.; Czarniecka, A. Coexistence of TERT Promoter Mutations and the BRAF V600E Alteration and Its Impact on Histopathological Features of Papillary Thyroid Carcinoma in a Selected Series of Polish Patients. Int. J. Mol. Sci. 2018, 19, 2647.

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