Inherited Brain Fitness Deficit caused by Light Stress Promotes Glioblastoma Progression in Drosophila

Environmental exposure including modern lifestyle habits and occupational exposures describe a wide spectrum of risk factors for human health including carcinogenesis. Glioblastoma is the most common, aggressive, and lethal type of glioma. It is highly proliferative and invasive, infiltrates the surrounding brain parenchyma and is resistant to current treatments. Patients suffering from glioblastoma have a wide heterogeneity in life expectancy, even with similar mutations, that can vary from weeks to years. Many potential risk factors for glioma have been studied to date, but few provide significant correlations for tumor prognosis. Here, we provide a novel perspective on the interaction between the tumor and host depending on paternal environmental or lifestyle determinants, coined as Brain fitness hypothesis. Permanent light exposure induces genetic stress hallmarks in the progeny that do not alter central nervous system development, but compromise Brain fitness to an accelerated glioma growth, ultimately reducing life expectancy. Reduced survival in the progeny correlates with an increase in the number of activated brain genes involved in neuronal dynamics as well as those relevant for glioma progression such as presynaptic, circadian genes or genes required for the tumoral network. Among the inheritable mechanisms, ncRNAs emerge as potential vectors for the transmission of parental exposure to the subsequent generations and might explain the complexity of inheritable traits and phenotypes acquired as a pleiotropic effect.