Highly recurrent TERT promoter mutations in human melanoma.

Science
Authors
Keywords
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.

Year of Publication
2013
Journal
Science
Volume
339
Issue
6122
Pages
957-9
Date Published
2013 Feb 22
ISSN
1095-9203
URL
DOI
10.1126/science.1229259
PubMed ID
23348506
PubMed Central ID
PMC4423787
Links
Grant list
T32 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