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: BACKGROUND
  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).
  
  
  METHODS
  We tested the mutation status by sequencing genomic tumor DNA and 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 had more available 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.
authors.affiliation: Laboratory for Cellular and Molecular Thyroid Research (X.S., R.L., G.Z., X.L., M.X.), Division of Endocrinology, Diabetes & Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Endocrinology & Metabolism (S.Q.), Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Pathology (J.B.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; 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; Department of Pathology (E.W.), The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China; Department of Medical Image (Y.L.), Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province 110001, China; Department of Pathology (X.Y.), Shengjing Hospital of China Medical University, Shenyang, Liaoning Province 110004, China; Department of Endocrinology (J.Z.), Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province 250021, China; Department of Endocrinology (J.D.), The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province 116011, China; Department of Pathology (A.K.E.-N.), University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; and The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases (X.S., Z.S., W.T.), Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Shi
authors.forename: Rengyun
authors.initials: R
authors.lastname: Liu
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
authors.forename: Guangwu
authors.initials: G
authors.lastname: Zhu
authors.forename: Justin
authors.initials: J
authors.lastname: Bishop
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
authors.forename: Yahong
authors.initials: Y
authors.lastname: Luo
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yang
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.forename: Jianling
authors.initials: J
authors.lastname: Du
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics* / Q000556:secondary*; D013964:Thyroid Neoplasms / Q000473:pathology*; D014633:Valine / Q000235:genetics
chemical_list: D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase; D014633:Valine