Epigenetic regulation of ZBTB18 promotes glioblastoma progression
Fedele V, Dai F, Masilamani AP, Heiland DH, Kling E, Gätjens-Sanchez AM, Ferrarese R, Platania L, Soroush D, Kim H, Nelander S, Weyerbrock A, Prinz M, Califano A, Iavarone A, Bredel M, Carro MS
Mol Cancer Res. online article
Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. This study characterizes the role of the putative tumor suppressor ZBTB18 and its regulation by promoter hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the mesenchymal subtype of GBM and provides a new mechanistic opportunity to specifically target this tumor subclass.
