title: Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation.
abstract: BACKGROUND
  Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations.
  
  
  METHODS
  We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers.
  
  
  RESULTS
  TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025).
  
  
  CONCLUSIONS
  The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations.
authors: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. drbae@catholic.ac.kr.
authors: Ja Seong
authors: JS
authors: Bae
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. chuchura@naver.com.|Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. chuchura@naver.com.
authors: Yourha
authors: Y
authors: Kim
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. thfk38@nate.com.|Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. thfk38@nate.com.
authors: Sora
authors: S
authors: Jeon
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. smilie21@naver.com.
authors: Se Hee
authors: SH
authors: Kim
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. kimecho@catholic.ac.kr.
authors: Tae Jung
authors: TJ
authors: Kim
authors: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. leesohee@catholic.ac.kr.
authors: Sohee
authors: S
authors: Lee
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. benedict@catholic.ac.kr.
authors: Min-Hee
authors: MH
authors: Kim
authors: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. ldj6026@catholic.ac.kr.
authors: Dong Jun
authors: DJ
authors: Lim
authors: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. lys9908@catholic.ac.kr.
authors: Youn Soo
authors: YS
authors: Lee
authors: Department of Hospital Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-gu, Seoul, 06591, Republic of Korea. ckjung@catholic.ac.kr.
authors: Chan Kwon
authors: CK
authors: Jung
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy / Q000556:secondary; D018276:Carcinoma, Medullary / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy / Q000556:secondary; D002291:Carcinoma, Papillary; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D003661:Decision Support Techniques; D005260:Female; D005787:Gene Frequency; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D056910:Republic of Korea; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase