The transcriptional landscape of CL-C tumors was further shaped by the activation of pivotal cell signaling pathways, mediated by STAT3 and RPS6KA1, for example, and epigenetic regulators, such as HDAC1, HDAC5, CBX4, and SUV39H2. The CL-C subclass was also characterized by the upregulation of several prominent genes, including DDIT4L, LGR6 (known to facilitate DNA repair and chemoresistance31,32), and ETNPPL (a negative regulator of glioma growth33). Here, CBX4 is linked to central nervous system cancer.