TERT promoter mutations
TERT promoter mutations affect the TERT promoter (located on the short arm of chromosome 5) which encodes for the hTERT component of telomerase, an enzyme which maintains and lengthens telomeres 4. Mutations that result in enhanced activity of telomerase, and therefore longer telomeres, can be is seen in over 50 different cancers throughout the body, including glioblastoma, follicular carcinomas of the thyroid, malignant melanoma, bladder transitional cell carcinoma, and hepatocellular carcinoma 2,3.
TERT promoter mutations, along with IDH mutations and 1p19q co-deletion status, has been recognized as an important prognostic marker for diffuse gliomas and is an important prognostic marker for diffuse gliomas.
It is encountered in all grades of diffuse gliomas, ranging from WHO grade II oligodendrogliomas (best prognosis) to WHO IV glioblastoma (worst prognosis), although the prevalence of TERT mutations varies significantly within different molecular groups; glioblastomas (IDH wildtype, 1p19q not co-deleted) and oligodendrogliomas (IDH mutant, 1p19q co-deleted) account for most cases 1.
Interestingly, the interaction of TERT mutations with IDH mutation status and 1p19q co-deletion status is not straightforward with various combinations having a strikingly different impact on survival 1. For example in IDH wild-type diffuse astrocytomas (not 1p19q co-deleted) of all grades (II to IV), having a TERT mutation significantly reduces survival, most striking on grade II and III tumors. It is also encountered in a significantly older age group than other molecular subgroups (~60-years-of-age) 1.
In contrast in IDH mutated diffuse gliomas, with or without 1p19q co-deletion, having a TERT mutation has only marginal impact on survival, and may actually be a positive prognostic factor 1.