Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis without an effective pharmacological treatment. Clinically, most patients present de novo grade IV lesions (primary GBMs), whereas only a small fraction of patients (5-10%) show progression from less aggressive WHO grade II diffuse astrocytomas and WHO grade III anaplastic astrocytomas (secondary GBMs). Very few data have been reported on the identification of grade-specific GBM biomarkers making the development of personalized treatments even more difficult. We explored the potential role of the X-chromosome cancer driver gene histone demethylase Lysine (K)-specific demethylase 5C (KDM5C) in GMB. KDM5C belongs to the KDM5 subfamily of JmjC (Jumonji C) domain-containing histone demethylases involved in various types of cancers including breast, colon, ovarian and prostate cancer. Specifically, this chromatin enzyme catalyzes the removal of the methyl groups from di- and tri-methylated lysine 4 on histone H3 (H3K4me2/3) in an Fe (II)- and ?-ketoglutarate-dependent manner. We carried out our studies on surgical excisions performed by fluorescence-guided surgery were isolated from an Italian cohort of GBM patients. Preliminary data allowed us to identify GBM patients with lower (KDM5Clow) and higher (KDM5Chigh) levels of KDM5C. A functional relationship between this chromatin enzyme and GBM signatures used in routine clinical practice has tested. Our study underlines the role of KDM5C in cancer and opens a new field of investigation in view of the possibility of validating this epigenetic enzyme as a new GMB biomarker.
Analysis of the X-chromosome cancer driver gene Lysine-specific demethylase 5C (KDM5C) in Glioblastoma Multiforme (GBM
Verrillo L;Miano MG;
2021
Abstract
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis without an effective pharmacological treatment. Clinically, most patients present de novo grade IV lesions (primary GBMs), whereas only a small fraction of patients (5-10%) show progression from less aggressive WHO grade II diffuse astrocytomas and WHO grade III anaplastic astrocytomas (secondary GBMs). Very few data have been reported on the identification of grade-specific GBM biomarkers making the development of personalized treatments even more difficult. We explored the potential role of the X-chromosome cancer driver gene histone demethylase Lysine (K)-specific demethylase 5C (KDM5C) in GMB. KDM5C belongs to the KDM5 subfamily of JmjC (Jumonji C) domain-containing histone demethylases involved in various types of cancers including breast, colon, ovarian and prostate cancer. Specifically, this chromatin enzyme catalyzes the removal of the methyl groups from di- and tri-methylated lysine 4 on histone H3 (H3K4me2/3) in an Fe (II)- and ?-ketoglutarate-dependent manner. We carried out our studies on surgical excisions performed by fluorescence-guided surgery were isolated from an Italian cohort of GBM patients. Preliminary data allowed us to identify GBM patients with lower (KDM5Clow) and higher (KDM5Chigh) levels of KDM5C. A functional relationship between this chromatin enzyme and GBM signatures used in routine clinical practice has tested. Our study underlines the role of KDM5C in cancer and opens a new field of investigation in view of the possibility of validating this epigenetic enzyme as a new GMB biomarker.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
