Abstract
INTRODUCTION
The revised version of the WHO classification system (2016) introduced molecular markers being of prognostic importance in gliomas. Primary spinal cord astrocytomas are very rare. Aggressive surgical resection is believed to be critical for extending progression free and overall survival. However, the prognostic significance of molecular variables remains unclear for these tumors. Herein we investigate molecular chances of spinal gliomas, which may allow more accurate risk stratification.
METHODS
We performed genome sequencing in 10 spinal astrocytomas undergoing surgical resection between 2000 and 2017. These spinal astrocytomas include glioblastomas (WHO grade IV), anaplastic astrocytomas (WHO grade III), diffuse astrocytomas (WHO grade II) and pilocytic astrocytoma (WHO grade I).
RESULTS
We identified 5 spinal glioblastomas, 1 anaplastic astrocytoma, 2 diffuse astrocytomas and 2 pilocytic astrocytomas. Median overall survival (OS) was 6 months (range: 2–14 months) for grade IV tumors, 33 months (range: 30–136 months) for grade II and III tumors and 95 months (range: 49–141 months) for grade I tumors, respectively. One grade II and one grade I tumor were carrying the IDH1 and IDH2 mutation, all other tumors were IDH wild type (OS: 93 vs. 10 months). Gross total resection was not achieved in any patient. 9 patients received adjuvant radiotherapy. The most current findings in spinal GBM were H3F3A mutations (5/5) and ATRX mutation (3/5). H3F3A mutation was observed in 1 WHO grade II tumor with a OS of 33 months. Mutation in H3F3A and WHO grade was associated with shortened OS in univariate analysis. WHO grade II tumors were found to have mutations in CCND2, DDX3X, EGFR, HIST1H3B, KIT, MYC, PDGFRA, PTCH2, SMARCA4 and TSC2.
CONCLUSION
Genomic analysis of spinal astrocytomas provides an opportunity to identify potential clinically relevant information. These data indicate an association between H3F3A mutation and a shortened overall survival in spinal astrocytomas.