Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition (HTA 2.0)

Intra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome. Affymetrix HTA 2.0 array analyses were performed according to the manufacturer's directions on total RNA extracted from 115 clonal malignant glioma cultures and 6 bulk cultures representing the parental material used to derive clones. 25 bilogical replicates were also included.