PATH-40. PROFILING PLEOMORPHIC XANTHROASTROCYTOMA WITH DNA METHYLATION AND EXPLORING THE TUMOR IMMUNE CELL-TYPE COMPOSITION WITH METHYLATION-BASED DECONVOLUTION

Abstract

Abstract INTRODUCTION Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that commonly affects children and young adults. PXAs are typically characterized by tumor lymphocytic infiltration, but the significance of the tumor immune microenvironment has not yet been well-defined. In this study, we correlated DNA methylation profiling of PXAs with clinical outcome and explored the tumor microenvironment by analyzing inflammatory cell populations. METHODS We retrospectively analyzed 30 tumor samples, of which 21 tumor samples from 18 subjects had a diagnosis of PXA both by DNA methylation and by histology. MethylCIBERSORT was used to deconvolute PXA inflammatory cell populations and compare them with inflammatory cell populations in previously published cohorts of IDH wildtype glioblastoma and ganglioglioma samples. RESULTS Median age at diagnosis was 16 years (range 7–32). 3-year and 5-year overall survival (OS) was 73% and 71% respectively. CDKN2A/B deletion was noted in 15 out of 18 subjects (83%). 10 out of the 12 subjects (83%) that had testing for BRAFV600E showed the mutation. CDKN2A/B deletion and Trisomy 7 did not show any significant association with overall survival (p = 0.39 and p = 0.69). Decreased survival was observed in subjects with tumors lacking the BRAFV600E mutation (p = 0.03). PXAs were observed to have significantly increased CD8 T-cell epigenetic signatures compared to gangliogliomas (p = 0.0019) and significantly increased CD8 T-cell and CD19 B-cell signatures compared to IDH wildtype glioblastomas (p = 0.0011 and p = 0.0011). CONCLUSION This research suggests that PXAs have a distinct methylation profile that correlates with clinical outcome. PXAs show significant upregulation of CD8 T-cell epigenetic signatures compared to gangliogliomas and significant upregulation of CD8 T-cell and CD19 B-cell epigenetic signatures compared to IDH wildtype glioblastomas. This distinct characterization of immune cell-types in PXAs could have an impact on future development of immunotherapy.