Molecular refinement of pilocytic astrocytoma in adult patients

• Verfasst von: Bode, Helena [VerfasserIn]
• Verfasst von: Kresbach, Catena [VerfasserIn]
• Verfasst von: Holdhof, Dörthe [VerfasserIn]
• Verfasst von: Dorostkar, Mario M. [VerfasserIn]
• Verfasst von: Harter, Patrick Nikolaus [VerfasserIn]
• Verfasst von: Hench, Jürgen Christian Hans [VerfasserIn]
• Verfasst von: Frank, Stephan [VerfasserIn]
• Verfasst von: Suwala, Abigail Kora [VerfasserIn]
• Verfasst von: Schweizer, Leonille [VerfasserIn]
• Verfasst von: Eckhardt, Alicia [VerfasserIn]
• Verfasst von: Neyazi, Sina [VerfasserIn]
• Verfasst von: Bockmayr, Michael [VerfasserIn]
• Verfasst von: Wefers, Annika K. [VerfasserIn]
• Verfasst von: Schüller, Ulrich [VerfasserIn]
• Titel: Molecular refinement of pilocytic astrocytoma in adult patients
• Verf.angabe: 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
• E-Jahr: 2024
• Jahr: February 2024
• Umfang: 10 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 19. Dezember 2023 ; Gesehen am 18.03.2024
• Titel Quelle: Enthalten in: Neuropathology & applied neurobiology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1975
• Jahr Quelle: 2024
• Band/Heft Quelle: 50(2024), 1, Artikel-ID e12949, Seite 1-10
• ISSN Quelle: 1365-2990
• DOI: doi:10.1111/nan.12949
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: BRAF
• Sach-SW: classification
• Sach-SW: DNA methylation
• Sach-SW: glioma
• Sach-SW: histology
• Sach-SW: pilocytic astrocytoma
• K10plus-PPN: 1883723116

Abstract

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).