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

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.

Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis

“…Among 51 studies of overall DTC, 39 [11,[14][15][16][17][18][19][20], 26 [11, 14-17, 19, 20, 26-28, 32, 35, 36, 38-41, 44, 45, 47, 48, 51, 53, 54, 56, 57], 19 [11, 14-16, 19, 20, 27, 32, 35, 36, 44, 45, 47, 48, 53, 54, 56-58], 20 [17, 19, 20, 27, 30, 31, 34-37, 40, 42, 46-48, 51, 54, 55, 59, 60], 11 [16,17,20,28,31,37,44,50,55,57,60] [16-18, 20, 27, 28, 30, 31, 33, 35-38, 42, 43, 46, 56, 58, 60, 62, 64-67], and 14 [14,16,18,20,26,28,29,39,42,46,47,60,66,68] studies were analyzed for the associations between TERT promoter mutation and gender, mean age, mean tumor size, multifocality, vascular invasion, extrathyroidal extension, LNM, distant metastasis, advanced TNM stage, persistence/recurrence, and diseasespecific mortality, respectively. Among 41 studies of PTC, 32 [11, 14-19, 27-31, 33, 35-40, 42, 43, 45-47, 49-56], 19 [11, 14-17, 19, 27, 28, 35, 36, 38-40, 45 [17, 18, 27, 28, 30, 31, 33, 35-37, 39, 42, 43, 46, 56, 58, 62, 64, 66], and 10 [14,16,…”

Relevance and clinicopathologic relationship of BRAF V600E, TERT and NRAS mutations for papillary thyroid carcinoma patients in Northwest China

“…Systematic review was conducted to explore the impact of double gene mutations on clinicopathological features. Fifteen studies with 5057 participants, from inception to October 2018 were included [9,12,[14][15][16][17][18][19][20][21][22][23][24][25][26]. Statistically meaningful association was found between BRAF V600E /TERT promoter co-mutations and lymph node metastasis (OR = 2.24, 95%CI = 1.53-3.29, P < 0.01, I 2 = 8%, Fig.…”

Genetyczne podłoże nowotworów tarczycy – wybrane zagadnienia

“…Niezdiagnozowany rak brodawkowaty rozprzestrzenia się drogą układu limfatycznego, tworząc przerzuty w obrębie narządu oraz okolicznych węzłów chłonnych. Wznowa występuje u 15% chorych, natomiast występowanie przerzutów odległych dotyczy tylko 5% przypadków [1,5].…”

“…Występowanie mutacji powoduje zmianę konformacji białka skutkującą zablokowanie jej w formie stale aktywnej, co powoduje stałe fosforylowanie i aktywowanie kinazy MAP2K1. Podobnie jak w przypadku mutacji w genach RAS skutkuje to stałym pobudzaniem ścieżki sygnałowej MAPK/Erk, niezależnie od czynników zewnątrzkomórkowych [5,15,17].…”