title: Prognostic Significance of TERT Promoter Mutations in Papillary Thyroid Carcinomas in a BRAF(V600E) Mutation-Prevalent Population.
abstract: The role of telomerase reverse transcriptase (TERT) promoter mutations in differentiated thyroid cancer has been well established. These mutations have a significantly higher prevalence in aggressive thyroid tumors, including widely invasive oncocytic carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas. Interestingly, in some studies, TERT mutations were found to be more common in tumors with a BRAF(V600E) mutation. However, mutational analysis of TERT promoter mutations in thyroid tumors has not been previously performed for patients in Korea, where the BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is particularly prevalent. This study analyzed TERT promoter mutations in various thyroid tumors and examined their relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases.
  
  
  
  Using 242 preoperative fine-needle aspiration biopsy specimens (including 207 PTCs) with confirmed histopathological diagnosis of the biopsied thyroid nodules, the TERT promoter status (C228T and C250T) was analyzed, and the relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases was examined.
  
  
  
  Of 242 patients, 14.5% (30/207), 26.7% (4/15), 50% (1/2), and 60% (2/5) of PTCs, follicular thyroid carcinomas, poorly differentiated carcinomas, and anaplastic thyroid carcinomas harbored a TERT(C228T) mutation, respectively. The TERT(C228T) mutation was associated with recurrence (p = 0.03). However, no association with other clinicopathologic factors in PTC was found. Coexistence of TERT(C228T) and BRAF(V600E) mutations was found in 13.0% of PTCs and was significantly associated with older age and advanced stage compared with the group negative for either mutation. The TERT(C228T) mutation status was an independent prognostic factor for recurrence-free survival (hazard ratio = 3.08 [confidence interval 1.042-9.079]; p = 0.042) in patients with PTC in multivariate analysis.
  
  
  
  Identification of TERT promoter mutations in preoperative fine-needle aspiration biopsy specimens may help in better characterizing the prognosis and triaging thyroid cancer patients for appropriate treatment.
authors.affiliation: 1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: 1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Tae Sook
authors.initials: TS
authors.lastname: Hwang
authors.affiliation: 4 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul, Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: 1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Han
authors.affiliation: 1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Wan Seop
authors.initials: WS
authors.lastname: Kim
authors.affiliation: 1 Department of Pathology, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Jang
authors.affiliation: 2 Department of Internal Medicine, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Suk Kyeong
authors.initials: SK
authors.lastname: Kim
authors.affiliation: 3 Department of Surgery, Konkuk University School of Medicine , Seoul, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yang
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics; D000328:Adult; D044466:Asian People / Q000235:genetics; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D056910:Republic of Korea; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase