Tmod-36. gene expression analysis of short and long survival groups of glioblastoma patient-derived orthotopic xenografts

Few molecular markers predictive of glioblastoma patient prognosis are MGMT promoter methylation, IDH1/2 mutation and G-CIMP status. Gene expression, on the other hand, has been less robust in predicting survival, in part due to the influence and variability of the hosts. Here we present analysis of gene expression patterns in relation to glioblastoma tumor aggressivity in uniform murine hosts, using glioblastoma patient-derived xenograft (PDX) models. Neurosphere cultures established from IDH1/2 wildtype glioblastomas were implanted orthotopically in cohorts of 10 to 15 nude mice, for development of PDX. Mice were monitored and sacrificed when symptomatic. Five PDX lines, presenting median survival of 29 to 59 days were classified as short (S) survivors, and 5 lines with median survival between 111 and 134 days as long (L) survivors. Mean patient age at diagnosis was 56 years and 55 years for the L and S PDX groups, respectively. Total RNA was extracted from PDX terminal tumors (3 biological replicates) and sequenced using Illumina HiSeq 2000 in a paired-end read format. RNA sequencing BAM files were generated and gene expression was measured as RPKM. Mouse reads were filtered out using Xenome. Differential gene expression analysis between tumors in S and L survival groups was conducted using the lmFit and eBayes, and genes were ranked by Benjamini-Hochberg adjusted P-values, set to adj.p<0.05, resulting in 1663 genes upregulated and 1539 genes downreg...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research