The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology

Purpose Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. Methods We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. Results The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients >= 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. Conclusions Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.