Studies on gliomas suggested that the microenvironment of human gliomas contains both glioma stem cells (GSCs) and glioma associated (GA)-mesenchymal stem cells (MSCs; (GA-MSCs). Also, studies have suggested that nano- sized vesicles, termed exosomes, have been recently observed to contribute towards intercellular communication within the tumor niche 1).
Gliomas are the second most common primary brain tumors, with an incidence of 4–5/100 000 individuals. Gliomas are the second leading cause of cancer mortality in adults under the age of 35, the fourth leading cause in those under the age of 54, and result in death in approximately 13 770 individuals per year in the United States.
The are more frequent among males 3).
They encompass two principle subgroups: diffuse gliomas and gliomas showing a more circumscribed growth pattern ('non-diffuse gliomas'). In the revised 4th edition of the World Health Organization Classification of Tumors of the Central Nervous System published in 2016, classification of especially diffuse gliomas has fundamentally changed: for the first time a large subset of these tumours is now defined based on presence/absence of IDH mutation and 1p/19q codeletion. Following this approach, the diagnosis of (anaplastic) oligoastrocytoma can be expected to largely disappear 4).
Sorting and grading of glial tumors by the WHO grade classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular biomarkers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neurooncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in elderly glioblastoma 5).
see Glioma Diagnosis.
see MRI for glioma.
see Glioma treatment.
see Glioma outcome.
see Glioma Books.
From 2012 to 2015, 94 Czech patients with primary brain tumors were enrolled into the study. The IDH1/2 mutation was detected by denaturing capillary electrophores. The methylation status of the MGMT gene and other 46 genes was revealed by MS-MLPA. In all 94 patients, the clinical data were correlated with molecular markers by Kaplan Meier analyses and Cox regression model. The MGMT promoter methylation status was established and compared to clinical data. In our study eight different probes were used to elucidate the MGMT methylation status; hypermethylation was proclaimed if four and more probes were positive. This 3 : 5 ratio was tested and confirmed by Kaplan-Meier and Cox analyses. The study confirmed the importance of the IDH1/2 mutation and hypermethylation of the MGMT gene promoter being present in tumour tissue. Both markers are independent positive survival predictors; in the Cox model the IDH hazard ratio was 0.10 and in the case of MGMT methylation it reached 0.32. The methylation analysis of the panel of additional 46 genes did not reveal any other significant epigenetic markers; none of the candidate genes have been confirmed in the Cox regression analyses as an independent prognostic factor 6).