PT  - JOURNAL ARTICLE
AU  - Huang, Franklin W.
AU  - Hodis, Eran
AU  - Xu, Mary Jue
AU  - Kryukov, Gregory V.
AU  - Chin, Lynda
AU  - Garraway, Levi A.
TI  - Highly Recurrent <em>TERT</em> Promoter Mutations in Human Melanoma
AID  - 10.1126/science.1229259
DP  - 2013 Feb 22
TA  - Science
PG  - 957--959
VI  - 339
IP  - 6122
4099  - http://science.sciencemag.org/content/339/6122/957.short
4100  - http://science.sciencemag.org/content/339/6122/957.full
SO  - Science2013 Feb 22; 339
AB  - 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.