P04.02.A CEREBELLAR GLIOMA WITH BRAF ACTIVATION: A MOLECULARY DISTINCT GLIOMA SUBGROUP WITH MAPK ACTIVATION

Abstract

Abstract BACKGROUND Rendering the correct tumor diagnosis is key to optimise cancer therapies and to orient patients and relatives regarding prognosis and general understanding of the disease. With the rising impact of molecular diagnostics more molecular profiles of tumors are being generated and assembled in central institutes. With this critical data assembly in world-wide repositories such as www.molecularneuropathology.org, new tumor groups with differing prognosis and driver alterations can be discerned. MATERIAL AND METHODS By analysing the epigenetic profiles from over 125.000 CNS tumor samples a distinct group of cases was identified (n=24). The samples in this group did not match an established reference methylation class in the Heidelberg brain tumor classifier (version 12.5). In a first analysis with the clinical data external suppliers have provided, these tumors are located in the cerebellum and typically in children (mean age = 9 years). RESULTS The variable histology ranged from low grade glial/glioneuronal appearances such as pilocytic astrocytoma (n= 12), ganglioglioma (n= 4), gangliocytoma (n= 1) to ependymoma (n= 2) and anaplastic ependymoma (n=1). For some cases just a descriptive histopathological diagnosis could be rendered (n= 6). A prominent feature in radiology and histology were micro- and macrocalifications (n =5). From 24 cases, 17 tumors (89% of all analysed tumors) harboured a BRAF V600E mutation. One case revealed a PRKAR2B:BRAF fusion. 6 cases could not be analysed because no remaining tumor material was available. While clinical follow-up data collection is still maturing, relapses were reported in 2 patients, and stable disease was reported in 12 cases. For 10 cases no follow up data is available, yet. CONCLUSION We found an epigenetically distinct group of childhood brain tumors located in the posterior fossa with an enrichment of BRAF V600E mutations. Clinical follow-up is yet to be evaluated, but recurrence was observed in a proportion of patients with available follow-up.