P10.02.B The fragile balance between proliferation and neoplasia in neural stem cells: role of DIAPH3 in glioblastoma

Abstract Background DIAPH3 belongs to the formin family of proteins that are master regulators cell cytoskeleton. plays a key role in cytokinesis as well karyokinesis. Hence, mouse brain, DIAPH3-deficient neural stem cells exhibit abnormal division leading aneuploidy and apoptosis progeny. Given importance cancer development progression, we asked whether loss could be involved genesis aggressiveness brain tumors. Material Methods We co-inactivated Diaph3 Trp53 genes cerebral cortex using Emx1-Cre line (Diaph3/Trp53 dcKO). As control, inactivated only gene same Cre (Trp53 cKO). Mouse survival was analyzed, tumors were collected for histological analysis molecular characterization. Additionally, measured expression human glioblastoma samples studied its impact on patient overall survival. Results Diaph3/Trp53 dcKO develop earlier compared cKO resulting decrease Hematoxylin-eosin staining, GFAP, OLIG2 KI67 immunostainings strongly suggest glioblastomas. Quantitative reverse transcription PCR performed biopsies from 73 patients uncover variable levels samples. Interestingly, multivariate Cox proportional-hazards shows low predicts worse survival, independently other known prognosis factors. Conclusion On one hand, our study favors mouse, suggesting tumor-suppressor DIAPH3. clinical has negative indicating may favor resistance chemotherapy and/or radiotherapy.