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

Yasuki Suruga, Kaishi Satomi, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Naoya Kemmotsu, Ryoji Imoto, Ryo Mizuta, Yusuke Tomita, Takao Yasuhara, Kana Washio, Hiroyuki Yanai, Yuko Matsushita, Yuko Hibiya, Akihiko Yoshida, David CapperKoichi Ichimura, Isao Date

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalJournal of neuro-oncology
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • DNA methylation
  • Elderly
  • High-grade astrocytoma with piloid features
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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