• Xiaoli Liu, Shen Qu, Rengyun Liu, Chunjun Sheng, Xiaoguang Shi, Guangwu Zhu, Avaniyapuram Kannan Murugan, Haixia Guan, Hongyu Yu, Yangang Wang, Hui Sun, Zhongyan Shan, Weiping Teng, and Mingzhao Xing.
• Laboratory for Cellular and Molecular Thyroid Research (X.L., R.L., X.S., G.Z., A.K.M., M.X.), Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Endocrinology & Metabolism (S.Q., C.S.), Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Endocrinology & Metabolism and Institute of Endocrinology (H.G., Z.S., W.T.), The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Department of Pathology (H.Y.), Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China; Department of Endocrinology & Metabolism (Y.W.), The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong Province 266003, China; and Jilin Provincial Key Laboratory of Surgical Translational Medicine (H.S.), Department of Thyroid and Parathyroid Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin Province 130033, China.
• J. Clin. Endocrinol. Metab. 2014 Jun 1; 99 (6): E1130-6.

ContextPromoter mutations chr5:1,295,228C>T and chr5:1,295,250C>T (termed C228T and C250T, respectively) in the gene for telomerase reverse transcriptase (TERT) have been reported in various cancers and need to be further investigated in thyroid cancer.ObjectiveThe aim of the study was to explore TERT promoter mutations in various thyroid tumors and examine their relationship with BRAF V600E mutation, iodine intake, and clinicopathological behaviors of thyroid cancer.DesignTERT promoter and BRAF mutations were identified by sequencing genomic DNA of primary thyroid tumors from normal- and high-iodine regions in China, and clinicopathological correlation was analyzed.ResultsThe C228T mutation was found in 9.6% (39 of 408) of papillary thyroid cancer (PTC), C250T was found in 1.7% (7 of 408) of PTC, and they were collectively found in 11.3% (46 of 408) of PTC. C228T was found in 31.8% (7 of 22) and C250T in 4.6% (1 of 22) of follicular thyroid cancer (FTC), and they were collectively found in 36.4% (8 of 22) of FTC. No TERT mutation was found in 44 benign thyroid tumors. The two mutations occurred in 3.8% (6 of 158) of BRAF mutation-negative PTC vs 16.0% (40 of 250) of BRAF mutation-positive PTC (P = 5.87 × 10(-4)), demonstrating their association. Unlike BRAF mutation, TERT promoter mutations were not associated with high iodine intake, but they were associated with older patient age, larger tumor size, extrathyroidal invasion, and advanced stages III/IV of PTC. Coexisting TERT and BRAF mutations were even more commonly and more significantly associated with clinicopathological aggressiveness.ConclusionsIn this large cohort, we found TERT promoter mutations to be common, particularly in FTC and BRAF mutation-positive PTC, and associated with aggressive clinicopathological characteristics.

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