Highly Recurrent TERT Promoter Mutations in Human Melanoma
Menées sur des lignées cellulaires et des échantillons tumoraux prélevés sur des patients atteints d'un mélanome, ces deux études identifient la présence fréquente de mutations dans la séquence promotrice du gène TERT
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.
Science , résumé, 2013