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

J Neurooncol. 2022 Oct;160(1):179-189. doi: 10.1007/s11060-022-04131-3. Epub 2022 Sep 15.

Abstract

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.

Keywords: DNA methylation; Elderly; High-grade astrocytoma with piloid features; Pilocytic astrocytoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Astrocytoma* / pathology
  • Brain Neoplasms* / pathology
  • Child
  • Child, Preschool
  • DNA Methylation
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Middle Aged
  • Mutation
  • Retrospective Studies
  • Young Adult

Substances

  • Isocitrate Dehydrogenase