BIOM-34. GENOMIC PROFILING IDENTIFIED COPY NUMBER VARIATIONS OF CDK4/6 AS A NOVEL PROGNOSTIC BIOMARKER FOR THALAMIC GLIOMA

Abstract

Abstract BACKGROUND Thalamic glioma is a rare tumor, which is poorly understood in adults. The genetic variation of this tumor is still unknown. In this study, we investigated the mutation landscape of thalamic glioma and compared the clinical outcomes between different mutation situations in thalamic glioma. METHODS Next-generation sequencing targeting 425 cancer-relevant genes was performed with 34 thalamic glioma tissue samples. Gene mutations and copy number variations were investigated for prognostic effect with overall survival data. RESULTS Several diagnostic and prognostic biomarkers appeared in our thalamic glioma cohort, including TP53 (56%), EGFR (41%), TERT (35%), M CL1 (26%), PDGFRA (26%), PTEN (26%), CDK4/6 (24%), POLE (24%), PIK3CA (24%), NF1 (21%), ATR (21%), ATRX (18%), BRAF (15%), and ROS1 (12%). Among all genetic aberrations with a more than 10% occurrence rate, two mutations (TERT and PTEN) were associated with poor overall survival and one copy number variation (CDK4/6) was associated with favorable overall survival (univariate P < 0.1). Among these genes, CDK4/6 copy number variations (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.035–0.704; P = 0.016) remained significant survival associated in multivariate analyses. Copy number variations of CDK4/6 was seldom reported as a prognostic biomarker for glioma, especially for thalamic glioma in public databases. Besides, several gene mutations (BRIP1, MRE11A, MAP2K1, ROS1, MUTYH, JARID2, CTCF, and EGFR) were found positively associated with CDK4/6 copy number variations. Gene enrichment analysis demonstrated that those genes were related to astrocyte differentiation. CONCLUSIONS In our study, CDK4/6 copy number variation was determined as a favorable overall survival biomarker for thalamic glioma, and CDK4/6 copy number variation associated mutant genes were related to astrocyte differentiation, which could be the potential therapeutic targets for thalamic glioma.