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Science DOI:10.1126/science.1229259

Highly recurrent TERT promoter mutations in human melanoma.

Publication TypeJournal Article
Year of Publication2013
AuthorsHuang, FW, Hodis, E, Xu, MJue, Kryukov, GV, Chin, L, Garraway, LA
Date Published2013 Feb 22
KeywordsBinding Sites, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Transformation, Neoplastic, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, Melanoma, Mutation, Promoter Regions, Genetic, Proto-Oncogene Proteins c-ets, Telomerase, Transcription, Genetic

Systematic sequencing of human cancer genomes has identified many recurrent mutations in the protein-coding regions of genes but rarely in gene regulatory regions. Here, we describe two independent mutations within the core promoter of telomerase reverse transcriptase (TERT), the gene coding for the catalytic subunit of telomerase, which collectively occur in 50 of 70 (71%) melanomas examined. These mutations generate de novo consensus binding motifs for E-twenty-six (ETS) transcription factors, and in reporter assays, the mutations increased transcriptional activity from the TERT promoter by two- to fourfold. Examination of 150 cancer cell lines derived from diverse tumor types revealed the same mutations in 24 cases (16%), with preliminary evidence of elevated frequency in bladder and hepatocellular cancer cells. Thus, somatic mutations in regulatory regions of the genome may represent an important tumorigenic mechanism.


Alternate JournalScience
PubMed ID23348506
PubMed Central IDPMC4423787
Grant ListT32 GM007753 / GM / NIGMS NIH HHS / United States
T32GM07753 / GM / NIGMS NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
DP2OD002750 / OD / NIH HHS / United States
DP2 OD002750 / OD / NIH HHS / United States
R33 CA126674 / CA / NCI NIH HHS / United States
R33CA126674 / CA / NCI NIH HHS / United States