Abstract

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Highlights

  • Since the revision of the WHO classification of central nervous tumors in 2016, molecular alterations are part of the integrated diagnosis of glial tumors [22]

  • A Lysine-27-to-methonine (K27M) mutation at one allele of histone H3 in histologically defined diffuse intrinsic pons gliomas (DIPG), midline gliomas and spinal cord astrocytomas has been found to be associated with an aggressive clinical course

  • All Patient characteristics In total 26 patients (19 male/7 female) with newly diagnosed astrocytomas were included with sufficient amount and quality of tissue for molecular analyses

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Summary

Introduction

Since the revision of the WHO classification of central nervous tumors in 2016, molecular alterations are part of the integrated diagnosis of glial tumors [22]. A Lysine-27-to-methonine (K27M) mutation at one allele of histone H3 in histologically defined diffuse intrinsic pons gliomas (DIPG), midline gliomas (such as thalamic tumors) and spinal cord astrocytomas has been found to be associated with an aggressive clinical course. This introduced the novel entity ‘diffuse midline glioma, Biczok et al acta neuropathol commun (2021) 9:119

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