Mutations in Diffuse Gliomas: An Update on Molecular Stratification, Prognosis, Recurrence, and Aggressiveness.

INTRODUCTION

is one of the most mutated oncogenes in solid tumors. In breast cancer (ER-positive, HER2-negative), these events represent a predictive biomarker of response to alpelisib. In glioblastomas (GBM), mutations were described as early constitutive events. Here, we investigated mutational profile across glioma molecular subgroups and its relevance during glioma recurrence. Furthermore, mutations' effect in PI3K pathway, prognosis, and response to therapy was also explored.

MATERIAL AND METHODS

Exons 10 and 21 of mutations were evaluated in 394 gliomas and 19 glioma recurrences from Instituto Português de Oncologia Lisboa Francisco Gentil (IPOLFG) and compared with The Cancer Genome Atlas (TCGA) data. TIMER2.0 and NetMHCpan4.1 were used to assess the immune-microenvironment contribution.

RESULTS

mutations were identified among all glioma subgroups, although with no impact on their stratification or prognosis. In both cohorts (IPOLFG and TCGA), mutation frequencies in -mutant and -wild-type GBM were similar (IPOLFG: 9% and 3%; TCGA: 8% and 2%). These mutations were not mutually exclusive with deletion and amplification. Despite their reduced frequency, we discovered mutations were maintained during glioma recurrence regardless of administered therapies. The immune microenvironment might not contribute to this phenotype as mutations did not influence immune cell infiltration.

CONCLUSIONS

Despite the absence of a predominant effect in glioma stratification, mutations were maintained during glioma recurrence, possibly contributing to glioma cell survival, representing promising therapeutic targets in recurrent glioma. Nevertheless, understanding the potential synergistic effects between mutations, deletion, and amplification is pivotal to targeted therapies' efficiency.