TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer

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, Michael Mingzhao Xing

Research output: Contribution to journalArticle

Abstract

Context: Promoter 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. Objective: The 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. Design: TERT 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. Results: The 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. Conclusions: In 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.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number6
DOIs
StatePublished - 2014

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Telomerase
Thyroid Neoplasms
Mutation
Tumors
Iodine
Thyroid Gland
Neoplasms
Genes
DNA
Papillary Thyroid cancer
DNA Sequence Analysis
China

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. / Liu, Xiaoli; Qu, Shen; Liu, Rengyun; Sheng, Chunjun; Shi, Xiaoguang; Zhu, Guangwu; Murugan, Avaniyapuram Kannan; Guan, Haixia; Yu, Hongyu; Wang, Yangang; Sun, Hui; Shan, Zhongyan; Teng, Weiping; Xing, Michael Mingzhao.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 6, 2014.

Research output: Contribution to journalArticle

Liu, Xiaoli ; Qu, Shen ; Liu, Rengyun ; Sheng, Chunjun ; Shi, Xiaoguang ; Zhu, Guangwu ; Murugan, Avaniyapuram Kannan ; Guan, Haixia ; Yu, Hongyu ; Wang, Yangang ; Sun, Hui ; Shan, Zhongyan ; Teng, Weiping ; Xing, Michael Mingzhao. / TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 6.
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title = "TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer",
abstract = "Context: Promoter 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. Objective: The 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. Design: TERT 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. Results: The 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. Conclusions: In 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.",
author = "Xiaoli Liu and Shen Qu and Rengyun Liu and Chunjun Sheng and Xiaoguang Shi and Guangwu Zhu and Murugan, {Avaniyapuram Kannan} and Haixia Guan and Hongyu Yu and Yangang Wang and Hui Sun and Zhongyan Shan and Weiping Teng and Xing, {Michael Mingzhao}",
year = "2014",
doi = "10.1210/jc.2013-4048",
language = "English (US)",
volume = "99",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
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TY - JOUR

T1 - TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer

AU - Liu, Xiaoli

AU - Qu, Shen

AU - Liu, Rengyun

AU - Sheng, Chunjun

AU - Shi, Xiaoguang

AU - Zhu, Guangwu

AU - Murugan, Avaniyapuram Kannan

AU - Guan, Haixia

AU - Yu, Hongyu

AU - Wang, Yangang

AU - Sun, Hui

AU - Shan, Zhongyan

AU - Teng, Weiping

AU - Xing, Michael Mingzhao

PY - 2014

Y1 - 2014

N2 - Context: Promoter 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. Objective: The 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. Design: TERT 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. Results: The 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. Conclusions: In 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.

AB - Context: Promoter 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. Objective: The 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. Design: TERT 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. Results: The 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. Conclusions: In 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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U2 - 10.1210/jc.2013-4048

DO - 10.1210/jc.2013-4048

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AN - SCOPUS:84902303028

VL - 99

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

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