CBIO-35THE ROLE OF Spt6 IN GLIOBLASTOMA MAINTENANCE AND THERAPEUTIC RESISTANCE

Glioblastoma multiforme (GBM) is among the most lethal of solid cancers in adults. It is associated with a median survival of only approximately 15 months despite aggressive radio- and chemotherapies and recurrence is inevitable. Despite recent advances in our understanding of this deadly disease, the molecular mechanism and/or genes that cause high recurrence rates and treatment resistance in GBM are poorly understood. Histone chaperones affect the structure of the chromatin and expression of genes through interaction with histones and RNA polymerase II (PolII). Spt6 is a highly conserved transcription elongation factor and histone chaperone that has been found to counteract tri- methylation of the histone variant H3, at various lysines, an otherwise epigenetic mark which is associated with repression of transcription. We have identified a novel role of Spt6 in glioblastoma cells. Our data show that siRNA-mediated knockdown of Spt6 in GBM cells results in decreased proliferation rates and progression through the cell cycle, increased levels of DNA damage (measured by γH2AX) as well as delayed capacity for DNA repair after exposure to ionizing radiation. Altogether, our data imply an important role of Spt6 in glioblastoma maintenance and therapeutic resistance.