TERT promoter mutation designates biologically aggressive primary glioblastoma

摘要

Large-scale molecular profiling efforts over the past decade have greatly clarified the molecular foundations of the diffuse gliomas, and the robust molecular subclasses of which they are composed.1 Mutations in IDH1/2 and ATRX, for instance, have emerged as prognostically relevant biomarkers that, along with MGMT promoter methylation and 1p/19q codeletion, are now routinely assessed at many institutions. Recently, mutations in the promoter region of the TERT gene, which encodes the enzymatic core of telomerase, were identified in a broad spectrum of cancers, including glioma. TERT promoter mutations are thought to unmask binding sites for ETS family transcription factors, upregulating TERT expression and cellular telomerase activity. As cancer cells have a basic need to maintain telomere length during many cycles of mitosis, enhanced telomerase activity would be expected to facilitate cellular immortalization and, in doing so, promote oncogenesis.