Highly Recurrent <i>TERT</i> Promoter Mutations in Human Melanoma

TLDR

Cancer genome sequencing has revealed recurrent pathogenic mutations in coding regions, and recent studies show that mutations also occur in gene regulatory regions such as promoters. In 70 melanomas, 71% carried one of two recurrent TERT promoter mutations that create new transcription factor binding sites and upregulate TERT expression, and a germline TERT promoter mutation was also identified in a melanoma‑prone family.

Abstract

Promoter Mutations and Cancer Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within the protein-coding regions of genes. Now, two studies suggest that the scope of mutations in human tumors extends to gene regulatory regions. In a study of 70 melanomas, Huang et al. (p. 957 , published online 24 January) found that 71% harbored one of two specific mutations in the promoter region of TERT , the gene coding for the catalytic subunit of telomerase, the enzyme that caps chromosome ends. Independently, Horn et al. (p. 959 , published online 24 January) identified a disease-segregating germline mutation in the TERT promoter in a family predisposed to melanoma and found additional TERT promoter mutations in a high percentage of sporadic melanomas and melanoma cell lines. The mutations in both studies generated new binding sites for specific transcription factors and, in reporter assays, caused an increase in transcription.