Longitudinal Characteristics of Glioblastoma in Genome-Wide Studies
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REVIEW
Longitudinal Characteristics of Glioblastoma in Genome-Wide Studies Zoltan Kraboth 1,2,3 & Bernadette Kalman 1,2,3 Received: 18 March 2019 / Accepted: 25 July 2019 # The Author(s) 2019
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. Keywords Glioblastoma . Sequential samples . Molecular evolution . Genomics . Transcriptomics . Epigenomics
Introduction Glioblastoma (GBM), a grade IV glioma according to the classification by the World Health Organization [WHO], is one of the most common, and most malignant brain tumors. The majority, 90% of GBM, is primary tumor arising de novo, while the remaining subset is secondary that progresses from a WHO grade II diffuse astrocytoma or WHO grade III anaplastic astrocytoma [1]. Characteristically, GMB recurs usually within a year despite aggressive therapy [2]. The standart treatment of newly diagnosed GBM involves radiotherapy and temozolomide (TMZ)-based chemotherapy following gross total resection * Bernadette Kalman [email protected]; [email protected] 1
Graduate School in Neurosciences, University of Pecs, 12. Szigeti street, Pecs 7624, Hungary
2
Institute of Laboratory Medicine, University of Pecs, 13. Ifjusag street, Pecs 7624, Hungary
3
Szentagothai Research Center, University of Pecs, 20. Ifjusag street, Pecs 7624, Hungary
[3]. These interventions somewhat slow the progression of the tumor, but inevitably, a small residual population of cells escapes surgery and chemoradiation, and results in a typically fatal recurrence in about 7 months after diagnosis [4]. In contrast to the initially diagnosed tumors, there is no standard treatment protocol for the recurrent GBMs as yet. With the currently avaiblable medications, the medi
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