Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.

Accumulating data shows that altered metabolic activity contributes to glioma development. Recently, modulation of SSADH (succinic semialdehyde dehydrogenase) expression, implicated in the catabolism of GABA neurotransmitter, was shown to impact glioma cell properties, such as proliferation, self-renewal and tumorigenicity. The purpose of this study was to investigate the clinical significance of SSADH expression in human gliomas.

Laying the groundwork for the Biobank of Rare Malignant Neoplasms at the service of the Hellenic Network of Precision Medicine on Cancer.

Biobanks constitute an integral part of precision medicine. They provide a repository of biospecimens that may be used to elucidate the pathophysiology, support diagnoses, and guide the treatment of diseases. The pilot biobank of rare malignant neoplasms has been established in the context of the Hellenic Network of Precision Medicine on Cancer and aims to enhance future clinical and/or research studies in Greece by collecting, processing, and storing rare malignant neoplasm samples with associated data.

Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase.

The Mixed Lineage Leukemia 2 (MLL2) protein, also known as KMT2B, belongs to the family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein of 2715 amino acids, widely expressed in adult human tissues and a paralog of the MLL1 protein. MLL2 contains a characteristic C-terminal SET domain responsible for methyltransferase activity and forms a protein complex with WRAD (WDR5, RbBP5, ASH2L and DPY30), host cell factors 1/2 (HCF 1/2) and Menin.

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues.

Histone Methyltransferase SETDB1: A Common Denominator of Tumorigenesis with Therapeutic Potential.

Epigenetic regulation of gene expression has been ultimately linked to cancer development, with posttranslational histone modifications representing attractive targets for disease monitoring and therapy. Emerging data have demonstrated histone lysine (K) methylation by methyltransferase SETDB1 as a common denominator of gene regulation in several cancer types. SETDB1 reversibly catalyzes the di- and trimethylation of histone 3 (H3) K9 in euchromatic regions of chromosomes, inhibiting gene transcription within these regions and promoting a switch from euchromatic to heterochromatic states.

Insights in the immunobiology of glioblastoma.

Glioblastoma, a grade IV astrocytoma, is considered as the most malignant intracranial tumor, characterized by poor prognosis and therapy resistance. Tumor heterogeneity that often leads to distinct functional phenotypes contributes to glioblastoma (GB) indispensable growth and aggressiveness. The complex interaction of neoplastic cells with tumor microenvironment (TME) along with the presence of cancer stem-like cells (CSCs) largely confers to extrinsic and intrinsic GB heterogeneity.

Paediatric gliomas: diagnosis, molecular biology and management.

Paediatric gliomas represent the most common brain tumour in children. Early diagnosis and treatment greatly improve survival. Histological grade is the most significant classification system affecting treatment planning and prognosis.

Chromatin remodeling defects in pediatric brain tumors.

Brain tumors are regarded as the most prevalent solid neoplasms in children and the principal reason of death in this population. Even though surgical resection, radiotherapy and chemotherapy have improved outcome, a significant number of patients die in 6-12 months after diagnosis while those who survive, frequently experience side effects and relapses. Several studies suggest that many types of cancer including pediatric brain tumors are characterized by alterations in epigenetic profiles with deregulated chromatin remodeling and posttranslational covalent histone modifications playing a prominent role.

Molecular Basis of Pediatric Brain Tumors.

Brain tumors emerge as the second commonest type of pediatric solid tumors following hematologic malignancies. Genomic profiling of low- and high-grade gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities and specific gene mutations which have been associated with aberrant activation of crucial signal transduction pathways, including mitogen-activated protein kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor signaling. Furthermore, pediatric high-grade gliomas are associated with chromatin remodeling defects and somatic histone gene mutations that affect prognosis.