Longitudinal Characteristics of Glioblastoma in Genome-Wide Studies

Abstract

Glioblastoma is one of the deadliest tumors with barely over one-year median survival despite intensive efforts in defining its molecular characteristics and searching for innovative treatment strategies. While major progress has been made in cataloging cross-sectional genomic, transcriptomic and epigenomic features of the tumor, and inferring its main molecular pathways and niches for potential targeted intervention, we still do not have sufficient knowledge concerning evolutionary patterns and dynamics of molecular changes or the treatment-induced effects affecting glioblastoma biology. In this review, we summarize the results of recent longitudinal genomic, transcriptomic and epigenomic studies that brought us closer to a better understanding of this lethal disease. Evidence suggests that neuronal / glioma stem cells with accumulating mutations initiate glioblastoma development and recurrence, but the hypothetical models describing the courses that lead to established tumors have not been fully proven. Moving from the histopathological phenotype to the results of high resolution OMICS studies, we try to synthesize the currently available information from sequential glioblastoma analyses in order to highlight its multifaceted features and heterogenetity, as well as the expected complexity of potential treatment strategies that might once succeed.

Single-cell landscapes of primary glioblastomas and matched explants and cell lines show variable retention of inter- and intratumor heterogeneity

“…While the molecular profiles of primary GBMs have been extensively studied (Brennan et al, 2013;Ceccarelli et al, 2016;Johnson et al, 2018), ultimately most patients succumb to recurrent disease. Given that recurrent tumors are often genetically and transcriptionally distinct from their primary tumors (Kraboth and Kalman, 2020), a better understanding of the molecular underpinnings of recurrent disease is crucial to improving outcomes for GBM. Two main factors make the study of recurrent GBM tumors particularly difficult: (1) only $25% of patients are eligible for repeat surgery upon recurrence (Weller et al, 2013), and (2) even resectable recurrent tumors tend to have a higher rate of necrosis, which can make molecular profiling difficult or impossible (Marucci et al, 2015).…”

Emerging Roles of NANOS RNA-Binding Proteins in Cancer

“…Another study showed the overexpression of NANOS3 in glioblastoma cell lines and tissues. Glioblastoma is the most common type of brain cancer that is characterized by high heterogeneity, mortality, and short median survival rate [ 39 ]. Moreover, molecular mechanisms leading to glioblastoma are not well understood.…”

Role of MRI in Differentiation between Postoperative Tumoral Recurrence and Radiation-Induced Brain Necrosis in Patients of Glioblastoma Multiform

“…Some studies speculate that distant recurrence 5 -10 years after the first operation is actually a new primary tumor; these tumors grow independently and may be caused by adjuvant radiotherapy or chemotherapy [26] [27]. However, other studies have found sufficient genetic similarity between distant recurrent tumors and primary tumors, suggesting that distant recurrent tumors are distant recurrence of primary tumors rather than independent primary GBM [28].…”