For example, a gain-of-function screen of epigenetic regulators identified circadian locomotor output cycles kaput (CLOCK, a gene amplified in approximately 5% of GBM cases) as a key hit in GSCs that not only promotes stemness but also triggers microglial infiltration and immunosuppressive polarization by transcriptionally upregulating olfactomedin-like 3 and legumain (LGMN). This evidence concerns the gene CLOCK and glioblastoma.