You are here

Science (New York, N.Y.) DOI:10.1126/science.1229259

Highly Recurrent TERT Promoter Mutations in Human Melanoma.

Publication TypeJournal Article
Year of Publication2013
AuthorsHuang, FW, Hodis, E, Xu, MJ, Kryukov, GV, Chin, L, Garraway, LA
JournalScience (New York, N.Y.)
Date Published2013/01/24

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 TERT, the gene coding for the catalytic subunit of telomerase, which collectively occur in 50 of 70 (71%) of melanomas examined. These mutations generate de novo consensus binding motifs for ETS transcription factors, and in reporter assays the mutations increased transcriptional activity from the TERT promoter by 2- to 4-fold. 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.