Telomerase reverse transcriptase (TERT) is the catalytic component of the telomerase complex, which plays a key role in maintaining the telomere length of chromosomes and cell immortality and in controlling cellular activities1. Mutations in the TERT promoter were found initially in melanoma2,3 and subsequently widely in other human cancers4, including thyroid cancer5,6. Two recurrent TERT promoter mutations located at hotspots chr5, 1,295,228 C > T (C228T) and 1,295,250 C > T (C250T) are particularly common, which correspond to the positions 124 and 146 bp, respectively, upstream of the translation start site of TERT; both mutations are predicted to generate a consensus binding site for E-twenty-six (ETS) transcription factors2,3. Further studies showed that TERT promoter mutations were associated with higher levels of TERT expression, telomerase activities, and oncogenic cellular activities7–10.