Genome and Computational Biology Lab, Mohanlal Sukhadia, University, Udaipur, Rajasthan, 313001, India.
Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031, Haryana, India.
Metab Brain Dis. 2024 Dec;39(8):1591-1611. doi: 10.1007/s11011-024-01414-8. Epub 2024 Aug 24.
The mostly aggressive and extremely malignant type of central nervous system is Glioblastoma (GBM), which is characterized by an extremely short average survival time of lesser than 16 months. The primary cause of this phenomenon can be attributed to the extensively altered genome of GBM, which is characterized by the dysregulation of numerous critical signaling pathways and epigenetics regulations associated with proliferation, cellular growth, survival, and apoptosis. In light of this, different genetic alterations in critical signaling pathways and various epigenetics regulation mechanisms are associated with GBM and identified as distinguishing markers. Such GBM prognostic alterations are identified in PI3K/AKT, p53, RTK, RAS, RB, STAT3 and ZIP4 signaling pathways, metabolic pathway (IDH1/2), as well as alterations in epigenetic regulation genes (MGMT, CDKN2A-p16CDKN2B-p15). The exploration of innovative diagnostic and therapeutic approaches that specifically target these pathways is utmost importance to enhance the future medication for GBM. This study provides a comprehensive overview of dysregulated epigenetic mechanisms and signaling pathways due to mutations, methylation, and copy number alterations of in critical genes in GBM with prevalence and emphasizing their significance.
中枢神经系统中最具侵袭性和极端恶性的类型是胶质母细胞瘤（GBM），其平均存活时间极短，不足 16 个月。造成这种现象的主要原因可以归因于 GBM 广泛改变的基因组，其特征是与增殖、细胞生长、存活和凋亡相关的许多关键信号通路和表观遗传学调控的失调。鉴于此，关键信号通路中的不同遗传改变和各种表观遗传学调控机制与 GBM 相关，并被确定为区分标志物。在 PI3K/AKT、p53、RTK、RAS、RB、STAT3 和 ZIP4 信号通路、代谢途径（IDH1/2）以及表观遗传调控基因（MGMT、CDKN2A-p16、CDKN2B-p15）中发现了这种 GBM 预后改变。探索专门针对这些通路的创新诊断和治疗方法对于提高 GBM 的未来药物至关重要。本研究全面概述了由于突变、甲基化和关键基因拷贝数改变导致的表观遗传机制和信号通路的失调，并强调了它们的重要性。
