Molecular refinement of pilocytic astrocytoma in adult patients

Helena Bode, Catena Kresbach, Dörthe Holdhof, Mario M Dorostkar, Patrick N Harter, Jürgen Hench, Stephan Frank, Abigail K Suwala, Leonille Schweizer, Alicia Eckhardt, Sina Neyazi, Michael Bockmayr, Annika K Wefers, Ulrich Schüller

Research output: Journal article (peer-reviewed)Journal article


AIM: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).

METHODS: We performed global DNA methylation profiling and DNA and RNA panel sequencing, and integrated the results with clinical data. We further compared the molecular characteristics of adult and paediatric PAs that had a significant match to one of the established PA methylation classes in the Heidelberg brain tumour classifier.

RESULTS: The mean age in our cohort was 33 years, and 43% of the tumours were located supratentorially. Based on methylation profiling, only 39% of the cases received a significant match to a PA methylation class. Sixteen per cent matched a different tumour type and 45% had a Heidelberg classifier score <0.9 with an affiliation to diverse established methylation classes in t-SNE analyses. Although the KIAA1549::BRAF fusion was found in 98% of paediatric PAs, this was true for only 27% of histologically defined and 55% of adult PAs defined by methylation profiling.

CONCLUSIONS: A particularly high fraction of adult tumours with histological features of PA do not match current PA methylation classes, indicating ambiguous histology and an urgent need for molecular profiling. Moreover, even in adult PAs with a match to a PA methylation class, the distribution of genetic drivers differs significantly from their paediatric counterparts (p<0.01).

Original languageEnglish
Article numbere12949
Pages (from-to)e12949
JournalNeuropathology and Applied Neurobiology
Issue number1
Early online date19 Dec 2023
Publication statusPublished - Feb 2024


  • BRAF
  • DNA methylation
  • classification
  • glioma
  • histology
  • pilocytic astrocytoma

ASJC Scopus subject areas

  • Neurology (clinical)
  • Neurology
  • Physiology (medical)
  • Pathology and Forensic Medicine
  • Histology


Dive into the research topics of 'Molecular refinement of pilocytic astrocytoma in adult patients'. Together they form a unique fingerprint.

Cite this