STAT3 is known to be the master regulator of mesenchymal differentiation in glioma cells (Carro et al., 2010), and, hence, this provides meaningful insights into the evolution of G-CIMP-low recurrent cells along the aberrant mesenchymal lineage transformation and into the unfavorable patient outcomes because these tumors can emerge as secondary GBMs. The gene discussed is STAT3; the disease is central nervous system cancer.