Two recent studies have associated mutations in the promoter region of the telomerase reverse transcriptase (TERTp) with short overall survival in glioblastoma. Increased telomerase activity has been previously shown to be typical in poor-prognosis, high-grade gliomas.

Genetic alterations associated with mean overall survival in glioblastoma. Credit: Image courtesy of M. Sanson.

Marc Sanson and co-workers assessed the potential prognostic value of TERTp mutations in patients with glioblastoma. “Our aim was to identify reliable prognostic biomarkers that could be easily transferable to daily clinical practice,” tells Sanson. The group found that two TERTp mutations—present in over 75% of the 395 glioblastoma biopsies analysed—were associated with poor overall survival.

In another study, Matthias Simon and colleagues analysed samples from 192 patients with glioblastoma, and also found a link between TERTp mutation status and survival. According to Simon, TERTp mutations are linked with a particularly aggressive clinical course, but if treated by a complete resection and temozolomide chemotheropy, the negative effect of TERTp mutation on prognosis is lost. Simon is curious about the 20% of glioblastoma cases that were TERTp-negative: “do these tumors harbour alternative genetic alterations?”

The findings by Sanson and colleagues suggest that in tumours without TERTp mutation, amplification of epidermal growth factor receptor gene (EGFR) is linked to poor prognosis. The results also corroborate previous findings that linked isocitrate dehydrogenase 1 (IDH1) mutation to prolonged overall survival, however, this effect was also found only in tumours without TERTp mutation.

“On the basis of these findings, we propose a very straightforward prognostic classification of glioblastoma,” Sanson comments. “This classification is based on the combination of three simple biomarkers and is suitable for clinical practice.” The results of these studies might also facilitate biomarker-based treatment selection. “TERTp mutations could turn out to be biomarkers for tumours that require more-aggressive surgery,” Simon concludes.