TERT promoter mutation

What it is

A TERT promoter mutation is a genetic change that increases activity of the TERT gene, which helps maintain telomeres — the protective caps on the ends of chromosomes. This allows tumor cells to keep dividing indefinitely. In adult diffuse astrocytic gliomas, a TERT promoter mutation is one of the molecular markers that can define glioblastoma.

Understanding TERT promoter mutation

Normally, telomeres shorten each time a cell divides, eventually limiting how many times a cell can divide. The TERT gene helps rebuild telomeres, and a TERT promoter mutation increases this activity, removing that limit and allowing tumor cells to divide without end. In the 2021 classification, an IDH-wildtype diffuse astrocytic glioma that has a TERT promoter mutation (or EGFR amplification, or combined chromosome 7 gain and 10 loss) is classified as glioblastoma — even if it does not yet show the most aggressive appearance. TERT promoter mutations also appear in oligodendrogliomas and other tumors, so their meaning depends on the context. Understanding the TERT promoter mutation clarifies a marker that helps tumor cells keep dividing and can define glioblastoma.

Why it matters

Understanding the TERT promoter mutation helps patients and families see one of the molecular markers used in diagnosis — it can define glioblastoma in IDH-wildtype tumors even before the most aggressive appearance develops.