Mutational analysis of patient-derived glioblastoma stem cells by whole-exome sequencing

Glioblastoma (GB) is the most malignant brain tumor with poor clinical outcome due to intrinsic resistance to conventional cytotoxic therapy. GB is notorious for the high degree of intratumour heterogeneity manifest as morpho-histological diversity of tumour cell types within the same tumor. The current biological paradigm for GB genesis and progression is centered on so-called glioblastoma stem cells (GSCs) implicated as the major source of intratumor heterogeneity and adaptability to cytotoxic insults imposed by conventional therapy consisting of combined radio- and chemotherapy. While comprising a minor population of GB cells GSCs play a major role in promoting GB progression especially after therapy. Therefore, delineation of mechanisms involved in the regulation of GSCs responses to cytotoxic and targeted therapies is a matter of clinical importance. In this project, a panel of GSCs has been isolated from human GB specimens and characterized with respect to the mutational status of genes coding for ALDH1A3, TP53 and IDH1/2, the proteins that have been implicated in the regulation of stemness, DNA damage response and metabolism.