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Highly recurrent TERT promoter mutations in human melanoma.

ABSTRACT: 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.

SUBMITTER: Huang FW

PROVIDER: S-EPMC4423787 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Highly recurrent TERT promoter mutations in human melanoma.

Huang Franklin W FW Hodis Eran E Xu Mary Jue MJ Kryukov Gregory V GV Chin Lynda L Garraway Levi A LA

Science (New York, N.Y.) 20130124 6122

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, ...[more]

PMID: 23348506

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TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

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TERT promoter mutations in melanoma survival.

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Germline TERT promoter mutations are rare in familial melanoma.

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| S-EPMC5288173 | biostudies-literature

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Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients.

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| S-EPMC5785756 | biostudies-literature

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| S-EPMC8469948 | biostudies-literature

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