Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients.

BACKGROUND

Molecular characteristics are essential for the classification and grading of gliomas. However, diagnostic classification of midline glioma is still debatable and substantial molecular and clinical heterogeneity within each subgroup suggested that they should be further stratified. Here, we studied the mutation landscape of Chinese midline glioma patients in hope to provide new insights for glioma prognosis and treatment.

METHODS

Tissue samples from 112 midline glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their somatic interactions and prognostic effect using overall survival data. Pathway-based survival analysis was performed for ten canonical oncogenic pathways.

RESULTS

We identified several currently established diagnostic and prognostic biomarkers of glioma, including (33%), (26%), (24%), (21%), (14%) (14%), (13%), and (6%). Among all genetic aberrations with more than 5% occurrence rate, six mutations and three copy number gains were greatly associated with poor overall survival (univariate, P < 0.1). Of these, mutations (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.37-6.61; P = 0.01) and mutations (HR, 2.04; 95% CI, 1.08-3.84; P = 0.02) remained significant in multivariate analyses. Additionally, we have also identified a novel amplification (found in 31% patients) as a potential independent biomarker for glioma (multivariate HR, 2.78; 95% CI, 1.53-5.08; P < 0.001), which was seldom reported in public databases. Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12-2.95; P = 0.01) and cell cycle pathways (HR, 1.97; 95% CI, 1.15-3.37; P = 0.01), both of which stayed meaningful after multivariate adjustment.

CONCLUSIONS

In this study, we discovered shorter survival in midline glioma patients with PIK3CA and TERT mutations and with abnormal PI3K and cell cycle pathways. We also revealed a novel prognostic marker, amplification that collectively provided new insights and opportunities in understanding and treating midline gliomas.