Mutations in the promoter of the telomerase gene TERT contribute to tumorigenesis by a two-step mechanism

Abstract

Two-step role for mutant TERT promoters Telomeres preserve genomic stability by preventing chromosomal fusions. The recent discovery that human tumors harbor mutations in the promoter region of the telomerase gene ( TERT ) produced a flurry of research aimed at elucidating the role of these mutations in cancer development. Chiba et al. present data that reconcile many of the conflicting results reported to date (see the Perspective by Shay). In human melanoma samples and a fibroblast model, TERT promoter mutations acted in two steps. First, the mutations allowed cells to proliferate with short telomeres. This fueled genomic instability and up-regulation of telomerase expression, leading to uncontrolled cell proliferation. Science , this issue p. 1416 ; see also p. 1358