title: TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant Metastatic Differentiated Thyroid Cancer.
abstract: Telomerase reverse transcriptase (TERT) promoter mutation has been reported to be associated with aggressive characteristics in differentiated thyroid cancer (DTC). This study examined the status of TERT mutation in distant metastatic DTC and evaluated the correlation between TERT mutation and radioiodine uptake, as well as that between TERT mutation and therapy response.
  
  
  
  TERT promoter and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in primary tumors of 66 patients with distant metastatic DTC. Stimulated thyroglobulin (sTg) changes, radioiodine uptake status (avid or nonavid), and other imaging evidence were analyzed to evaluate therapy response. After a median follow-up of 46.5 mo (interquartile range, 29.0-70.5 mo), therapy response was classified as either disease control or refractory.
  
  
  
  The prevalence of TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent (13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of the TERT mutation group. Of cases negative for both mutations, 78.12% (25/32) presented with decreased sTg. TERT mutation closely correlated with a poor response to radioiodine therapy (P < 0.001), and all 15 patients were classified as refractory to radioiodine therapy, with a positive predictive value of 100% at the endpoint of follow-up. TERT mutation was associated with older mean age at diagnosis (P < 0.001), larger mean tumor diameter (P = 0.013), and greater likelihood of both BRAF mutation coexistence (P = 0.044) and radioiodine-refractory character (P < 0.001). In the 36 cases whose imaging results underwent semiquantitative analysis, TERT mutation significantly correlated with non-radioiodine avidity, with a much lower mean tumor-to-background ratio (obtained from postradioiodine whole-body scanning) than in TERT wild-type cases (P < 0.001). In addition, patients with distant metastatic DTC with TERT mutation were more likely to lose radioiodine avidity at the initial radioiodine therapy than were those with only BRAF mutation (8/8 vs. 5/11; Fisher exact test, P = 0.018).
  
  
  
  TERT mutation closely associates with non-radioiodine avidity in distant metastatic DTC, and when compared with BRAF mutation, TERT mutation manifested a greater negative influence on radioiodine uptake. TERT mutation could also be used as an early predictor of radioiodine-refractory cases.
authors: Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xue
authors: X
authors: Yang
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Jiao
authors: J
authors: Li
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xiaoyi
authors: X
authors: Li
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; and.
authors: Zhiyong
authors: Z
authors: Liang
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Wen
authors: W
authors: Gao
authors: Department of Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
authors: Jun
authors: J
authors: Liang
authors: Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Shujun
authors: S
authors: Cheng
authors: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China linys@pumch.cn.
authors: Yansong
authors: Y
authors: Lin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000453:epidemiology / Q000532:radiotherapy* / Q000556:secondary*; D002681:China / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011836:Radiation Tolerance / Q000235:genetics; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D007457:Iodine Radioisotopes; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C509186:TERT protein, human; D019098:Telomerase
keywords: TERT mutation; differentiated thyroid carcinoma; radioactive iodine therapy; therapy response