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Bu, Rong; Siraj, Abdul K.; Divya, Sasidharan Padmaja; Kong, Yan; Parvathareddy, Sandeep Kumar; Al‐Rasheed, Maha; Al‐Obaisi, Khadija A.S.; Victoria, Ingrid G.; Al‐Sobhi, Saif S.; Al‐Dawish, Mohammed; Al‐Dayel, Fouad; Al‐Kuraya, Khawla S.
International journal of cancer, 15 May 2018, Letnik: 142, Številka: 10Journal Article
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation to cancer progression in PTC patients is still not fully understood. In this study, we investigated the incidence of TERT promoter mutations and TERT protein expression and their association with clinicopathological outcomes in a large cohort of PTC samples using direct sequencing technology and immunohistochemistry. Furthermore, two PTC cell lines were utilized to investigate role of TERT mutations in mediating metastasis. Two promoter hotspot mutations C228T and C250T were identified in 18.0% (167/927) of our cohort and were significantly associated with poor 5 years disease‐free survival and distant metastasis of PTC. TERT protein overexpression was noted in 20.1% of our PTC cohort and was significantly associated with poor prognostic markers such as older age, extrathyroidal extension and Stage IV tumors. A significant association was also found between TERT overexpression and epithelial–mesenchymal transition (EMT) markers. Functional analysis showed that TERT inhibition reduced cell growth, invasion, migration and angiogenesis in PTC via suppression of EMT in PTC cells. Our results suggest that TERT promoter mutation is an independent predictor of disease‐free survival and might drive the metastasis, and downregulation of TERT could potentiate antitumor and antimetastatic activities in PTC. What's new? Promoter mutation in the telomerase reverse transcriptase (TERT) gene has been identified as a prognostic marker in papillary thyroid carcinoma (PTC). However, the contribution of TERT promoter mutation to cancer progression in PTC patients is still not fully understood. Here, the authors analyzed TERT promoter mutation and protein expression in a cohort of almost 1000 Middle Eastern PTC patients. Altogether, the findings provide robust clinical and molecular evidence supporting the role of TERT alterations in PTC tumorigenesis and metastasis and offer a promising molecular target for developing therapeutic modalities.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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