Morphological and molecular characteristics of glioblastoma and the hopes of its treatment
Morphological and molecular characteristics of glioblastoma and the hopes of its treatment
shohreh shahmir,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: The most frequent primary brain tumor, glioblastoma multiforme (GBM), is classified as a grade IV astrocytoma by the World Health Organization (WHO), and it has a median survival time of roughly one year with current multi-modal therapies. Recent data reveal that the general category of gliomas accounts for about 30% of all primary and 80% of all malignant brain tumors, whereas 54% of all malignant brain tumors are GBM and arise at a rate of 3.20 per 100 000 person-years. The clinicopathological aspects of GBM exhibit significant variation, and recent research has raised the possibility that the existence of a cancer stem cell (CSC) population may both explain this heterogeneity and offer a mechanism for tumor recurrence and therapy resistance. The aim of this study was investigating Morphological and molecular characteristics of glioblastoma and the hopes of its treatment.
Methods: This study with the Morphological and molecular characteristics of glioblastoma and the hopes of its treatment by, Google Scholar, scientific databases including Science Direct, Springer, and PubMed.
Results: Results revealed severe dysregulation of PDGFRA's downstream molecular signaling pathways and copy number changes in the protein. Chromosome 1q gains were more common in HGG (30%) compared to adult GBM (9%) but chromosome 7 gains were more common in adult GBM (13% vs. 74%). Chromosome 10q losses were more prevalent in adult GBM (35% vs. 80%). Furthermore, HGG did not exhibit any IDH1 alterations. In HGGs exposed to radiation, chromosome 1q gain and PDGFRA amplification were more prevalent. Newly discovered key genes that play a role in HGG formation have brought attention to the distinct ways that this tumor develops in contrast to adult GBM.
In a recent groundbreaking study, 48 HGGs with matched germline tissue were subjected to whole-exome sequencing, which revealed 80 somatic mutations in tumors. Two single-nucleotide polymorphisms in H3F3A, which encodes the variant of the histone H3.3 protein involved in DNA organization, were found. 36% (32/90) of HGGs and just 3% (11/318) of young adult GBMs had H3F3A mutations. Interestingly. The majority of HGG also had mutations in p53, ATP-dependent helicase (ATRX), death-associated protein 6 (DAXX), which is involved in chromatin remodeling, and these mutations largely overlapped with H3F3A mutations.
Conclusion: The histological, clinical, and molecular understanding of GBM and its variants have advanced significantly. Impressive data regarding probable new variants and their differentiating characteristics have also been presented by recent studies. Nevertheless, in order to distinguish real variants from histopathological differentiation signs, new diagnostic and prognostic indicators of GBM variants are required. Finally, future investigations will require the use of uniform diagnostic criteria to define these developing variants. Understanding these GBM variations may help to clarify the mechanisms underlying the significant heterogeneity and therapeutic resistance of this disease. Last but not least, GBM continues to be an aggressive disease with a dismal prognosis and therapeutic options. Few effective treatments or biomarkers have been created, despite the large number of randomized studies that have been done to guide standard therapy for different illness presentations. A method to more effectively assess intriguing candidate medicines and biomarkers is required. New incentives for scientific discovery and investment in the disease are also required.