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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  BRA F 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.

Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation