10098- MPC-11 THE GENETIC DUET OF BRAF V600E AND TERT PROMOTER MUTATIONS IN ANAPLASTIC PLEOMORPHIC XANTHOASTROCYTOMAS AND EPITHELIOID GLIOBLASTOMAS

Abstract OBJECTIVE Pleomorphic xanthoastrocytoma (PXA), anaplastic PXA (aPXA), and epithelioid glioblastoma (E-GBM) are known to frequently harbor the BRAF V600E mutation and share numerous pathological and clinical similarities. This study investigates the molecular biological and clinical features of these tumors. METHODS Cases diagnosed morphologically as PXA/aPXA/E-GBM with reported BRAF V600E/TERT promoter (TERTp) mutations/prognostic outcomes were included. Information regarding tumor location, cerebrospinal fluid (CSF) dissemination, and CDKN2A/B co-deletions was also collected. RESULTS A total of 104 cases (54 females, 49 males, 1 unspecified; from 14 literature sources and 7 own cases) were included. Patients ranged from 5 to 80 years old (median age 39). PXA was observed in 32 cases (30.8%), aPXA in 27 cases (26.0%), and E-GBM in 45 cases (43.3%). Temporal lobe localization was found in PXA in 13/27 (48.1%) cases, aPXA in 6/18 (33.3%) cases, and E-GBM in 14/44 (31.8%) cases. The BRAF V600E mutation was identified in PXA 23/32 (71.9%), aPXA 21/27 (77.8%), and E-GBM 27/45 (60.0%). TERTp mutations were present in PXA 23/32 (0%), aPXA 6/27 (22.2%), and E-GBM 19/31 (61.3%). The oncogene duet (BRAF V600E and TERTp) was observed in 5/27 (18.5%) aPXA cases and 19/45 (42.2%) E-GBM cases. Median overall survival (MOS) was 160 months for PXA, 67 months for aPXA, and 12 months for E-GBM. The MOS for the oncogene duet group was 11 months. CSF dissemination was noted in 28 out of 32 (87.5%) E-GBM cases. DISCUSSION The oncogene duet was more prevalent in E-GBM compared to aPXA. Since more than half of the E-GBM cases did not show the oncogene duets, E-GBM is considered a heterogeneous group. Despite this heterogeneity, the high incidence of CSF dissemination and poor prognosis in E-GBM cases underscore the potential clinical significance of maintaining E-GBM as a distinct diagnostic category.