BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas

Abstract

BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.

Keywords: BRAF V600E; Brain stem neoplasms; Ganglioglioma; Growth; Prognosis.