TBIO-17. INTEGRATIVE ANALYSES OF BRAFv600e MUTATED GLIOMAS: FROM MOLECULAR BIOLOGY TO RADIOLOGY AND TREATMENTS

Abstract

BRAFv600e mutation is encountered mostly in low-grade pediatric gliomas (LGG) and epileptogenic glioneuronal tumors, such as gangliogliomas (GG). Less frequently this mutation is present in high-grade glial (HGG) or glioneuronal tumors. Recent publications were highlighting BRAF mutation and CDKN2A deletion, as independent prognostic factors linked to a worst outcome in LGGs. We studied retrospectively a monocentric cohort of 12 LGGs (9 GG and 3 pilocytic astrocytomas) and 9 HGG (5 “de novo” tumors and 4 with a long past of LGG evolution) with BRAFv600e positivity. The patients were aged from 1 to 47 years. LGGs were under 20 years and only 3 patients with HGGs had less than 18 years. We focused on extended tumors’ biology assessment by DNA single-cell analyses, RNAsequencing, NGS, metabolomics, radiology (MRI, PET-scanning and spectroscopy) and correlated them to tumor’s data. One LGG had a CDKN2A deletion. Six had a complete surgical resection, 2 had a minimal residue and 4 had chemotherapies after partial surgery and relapsed. All HGGs had a surgical resection followed by chemotherapy and radiotherapy and additional CDKN2A deletion. Two pediatric HGGs relapsed rapidly. Only one benefited positively from targeted therapy. Specific radiological and spectroscopic signs were linked to the BRAF mutation itself and those different groups (LGGs, HGGs and LGGs with long term evolution of HGG), where specific molecular pathways and metabolomic profiles are associated. Currently, we are going further in the correlations to be able to predict in LGG their potential long-term evolution, where MAPK pathway modulations might be involved.