Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer

Xiaoguang Shi, Rengyun Liu, Shen Qu, Guangwu Zhu, Justin Bishop, Xiaoli Liu, Hui Sun, Zhongyan Shan, Enhua Wang, Yahong Luo, Xianghong Yang, Jiajun Zhao, Jianling Du, Adel K. El-Naggar, Weiping Teng, Mingzhao Xing

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Abstract

Context: The aggressive role of TERT promoter mutations has been well established in differentiated thyroid cancer but has not been established in anaplastic thyroid cancer (ATC). Research Design: We tested the mutation status by sequencing genomic tumorDNAand examined its relationship with clinicopathological characteristics of ATC. Results: Among 106 American and Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in 37 (34.9%) cases, TERT promoter mutation 1,295,250 C>T was found in four cases (3.8%), and the two mutations were mutually exclusive and collectively found in 41 cases (38.7%). TERT C228T occurred in 28 of 90 (31.1%) wild-type BRAF cases vs nine of 16 (56.3%) BRAF V600E cases, with an odds ratio of 2.85 (95% confidence interval, 0.96-8.42; P =.05). Patient age was 67.6 ± 13.6 vs 61.6 ± 11.4 years in the TERT C228T vs wild-type TERT patients (P =.02), demonstrating an association between TERT C228T and older patient age. This association was also seen within the American cohort. In this cohort, which hadmoreavailable clinicopathological data, TERT C228T was associated with distant metastasis of the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3%) TERT C228T patients vs eight of 26 (30.8%) wild-type TERT patients, with an odds ratio of 11.25 (95% confidence interval, 2.53-50.08; P =.001). No association was found with patient sex, tumor size, lymph node metastasis, and extrathyroidal invasion of ATC. Conclusions: This is the largest study on the aggressive role of TERT promoter mutations in ATC, demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC.

Original languageEnglish (US)
Pages (from-to)E632-E637
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number4
DOIs
StatePublished - Jan 1 2015

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Tumors
Neoplasm Metastasis
Mutation
Odds Ratio
Confidence Intervals
Neoplasms
Anaplastic Thyroid Carcinoma
Thyroid Neoplasms
Research Design
Lymph Nodes

ASJC Scopus subject areas

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

Cite this

Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. / Shi, Xiaoguang; Liu, Rengyun; Qu, Shen; Zhu, Guangwu; Bishop, Justin; Liu, Xiaoli; Sun, Hui; Shan, Zhongyan; Wang, Enhua; Luo, Yahong; Yang, Xianghong; Zhao, Jiajun; Du, Jianling; El-Naggar, Adel K.; Teng, Weiping; Xing, Mingzhao.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 4, 01.01.2015, p. E632-E637.

Research output: Contribution to journalArticle

Shi, X, Liu, R, Qu, S, Zhu, G, Bishop, J, Liu, X, Sun, H, Shan, Z, Wang, E, Luo, Y, Yang, X, Zhao, J, Du, J, El-Naggar, AK, Teng, W & Xing, M 2015, 'Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 4, pp. E632-E637. https://doi.org/10.1210/jc.2014-3606
Shi, Xiaoguang ; Liu, Rengyun ; Qu, Shen ; Zhu, Guangwu ; Bishop, Justin ; Liu, Xiaoli ; Sun, Hui ; Shan, Zhongyan ; Wang, Enhua ; Luo, Yahong ; Yang, Xianghong ; Zhao, Jiajun ; Du, Jianling ; El-Naggar, Adel K. ; Teng, Weiping ; Xing, Mingzhao. / Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 4. pp. E632-E637.
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title = "Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer",
abstract = "Context: The aggressive role of TERT promoter mutations has been well established in differentiated thyroid cancer but has not been established in anaplastic thyroid cancer (ATC). Research Design: We tested the mutation status by sequencing genomic tumorDNAand examined its relationship with clinicopathological characteristics of ATC. Results: Among 106 American and Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in 37 (34.9{\%}) cases, TERT promoter mutation 1,295,250 C>T was found in four cases (3.8{\%}), and the two mutations were mutually exclusive and collectively found in 41 cases (38.7{\%}). TERT C228T occurred in 28 of 90 (31.1{\%}) wild-type BRAF cases vs nine of 16 (56.3{\%}) BRAF V600E cases, with an odds ratio of 2.85 (95{\%} confidence interval, 0.96-8.42; P =.05). Patient age was 67.6 ± 13.6 vs 61.6 ± 11.4 years in the TERT C228T vs wild-type TERT patients (P =.02), demonstrating an association between TERT C228T and older patient age. This association was also seen within the American cohort. In this cohort, which hadmoreavailable clinicopathological data, TERT C228T was associated with distant metastasis of the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3{\%}) TERT C228T patients vs eight of 26 (30.8{\%}) wild-type TERT patients, with an odds ratio of 11.25 (95{\%} confidence interval, 2.53-50.08; P =.001). No association was found with patient sex, tumor size, lymph node metastasis, and extrathyroidal invasion of ATC. Conclusions: This is the largest study on the aggressive role of TERT promoter mutations in ATC, demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC.",
author = "Xiaoguang Shi and Rengyun Liu and Shen Qu and Guangwu Zhu and Justin Bishop and Xiaoli Liu and Hui Sun and Zhongyan Shan and Enhua Wang and Yahong Luo and Xianghong Yang and Jiajun Zhao and Jianling Du and El-Naggar, {Adel K.} and Weiping Teng and Mingzhao Xing",
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T1 - Association of TERT promoter mutation 1,295,228 C>T with BRAF V600E mutation, older patient age, and distant metastasis in anaplastic thyroid cancer

AU - Shi, Xiaoguang

AU - Liu, Rengyun

AU - Qu, Shen

AU - Zhu, Guangwu

AU - Bishop, Justin

AU - Liu, Xiaoli

AU - Sun, Hui

AU - Shan, Zhongyan

AU - Wang, Enhua

AU - Luo, Yahong

AU - Yang, Xianghong

AU - Zhao, Jiajun

AU - Du, Jianling

AU - El-Naggar, Adel K.

AU - Teng, Weiping

AU - Xing, Mingzhao

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Context: The aggressive role of TERT promoter mutations has been well established in differentiated thyroid cancer but has not been established in anaplastic thyroid cancer (ATC). Research Design: We tested the mutation status by sequencing genomic tumorDNAand examined its relationship with clinicopathological characteristics of ATC. Results: Among 106 American and Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in 37 (34.9%) cases, TERT promoter mutation 1,295,250 C>T was found in four cases (3.8%), and the two mutations were mutually exclusive and collectively found in 41 cases (38.7%). TERT C228T occurred in 28 of 90 (31.1%) wild-type BRAF cases vs nine of 16 (56.3%) BRAF V600E cases, with an odds ratio of 2.85 (95% confidence interval, 0.96-8.42; P =.05). Patient age was 67.6 ± 13.6 vs 61.6 ± 11.4 years in the TERT C228T vs wild-type TERT patients (P =.02), demonstrating an association between TERT C228T and older patient age. This association was also seen within the American cohort. In this cohort, which hadmoreavailable clinicopathological data, TERT C228T was associated with distant metastasis of the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3%) TERT C228T patients vs eight of 26 (30.8%) wild-type TERT patients, with an odds ratio of 11.25 (95% confidence interval, 2.53-50.08; P =.001). No association was found with patient sex, tumor size, lymph node metastasis, and extrathyroidal invasion of ATC. Conclusions: This is the largest study on the aggressive role of TERT promoter mutations in ATC, demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC.

AB - Context: The aggressive role of TERT promoter mutations has been well established in differentiated thyroid cancer but has not been established in anaplastic thyroid cancer (ATC). Research Design: We tested the mutation status by sequencing genomic tumorDNAand examined its relationship with clinicopathological characteristics of ATC. Results: Among 106 American and Chinese ATC samples, TERT 1,295,228 C>T (termed TERT C228T) mutation was found in 37 (34.9%) cases, TERT promoter mutation 1,295,250 C>T was found in four cases (3.8%), and the two mutations were mutually exclusive and collectively found in 41 cases (38.7%). TERT C228T occurred in 28 of 90 (31.1%) wild-type BRAF cases vs nine of 16 (56.3%) BRAF V600E cases, with an odds ratio of 2.85 (95% confidence interval, 0.96-8.42; P =.05). Patient age was 67.6 ± 13.6 vs 61.6 ± 11.4 years in the TERT C228T vs wild-type TERT patients (P =.02), demonstrating an association between TERT C228T and older patient age. This association was also seen within the American cohort. In this cohort, which hadmoreavailable clinicopathological data, TERT C228T was associated with distant metastasis of the tumor; specifically, distant metastasis occurred in 15 of 18 (83.3%) TERT C228T patients vs eight of 26 (30.8%) wild-type TERT patients, with an odds ratio of 11.25 (95% confidence interval, 2.53-50.08; P =.001). No association was found with patient sex, tumor size, lymph node metastasis, and extrathyroidal invasion of ATC. Conclusions: This is the largest study on the aggressive role of TERT promoter mutations in ATC, demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC.

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U2 - 10.1210/jc.2014-3606

DO - 10.1210/jc.2014-3606

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