Abstract
PurposeGlioblastoma is the most aggressive form of brain tumors. A better understanding of the molecular mechanisms leading to its evolution is essential for the development of treatments more effective than the available modalities. Here, we aim to identify molecular drivers of glioblastoma development and recurrence by analyzing DNA CpG methylation patterns in sequential samples.MethodsDNA was isolated from 22 pairs of primary and recurrent formalin-fixed, paraffin-embedded glioblastoma specimens, and subjected to reduced representation bisulfite sequencing. Bioinformatic analyses were conducted to identify differentially methylated sites and pathways, and biostatistics was used to test correlations among clinical and pathological parameters.ResultsDifferentially methylated pathways likely involved in primary tumor development included those of neuronal differentiation, myelination, metabolic processes, synapse organization and endothelial cell proliferation, while pathways differentially active during glioblastoma recurrence involved those associated with cell processes and differentiation, immune response, Wnt regulation and catecholamine secretion and transport.ConclusionDNA CpG methylation analyses in sequential clinical specimens revealed hypomethylation in certain pathways such as neuronal tissue development and angiogenesis likely involved in early tumor development and growth, while suggested altered regulation in catecholamine secretion and transport, Wnt expression and immune response contributing to glioblastoma recurrence. These pathways merit further investigations and may represent novel therapeutic targets.
Highlights
Zoltan Kraboth and Bence Galik co-authors contributed to the paper.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Institute of Laboratory Medicine, School of Medicine, University of Pecs, Pecs, HungarySzentagothai Research Center, University of Pecs, 20
Differentially methylated pathways likely involved in primary tumor development included those of neuronal differentiation, myelination, metabolic processes, synapse organization and endothelial cell proliferation, while pathways differentially active during glioblastoma recurrence involved those associated with cell processes and differentiation, immune response, Wnt regulation and catecholamine secretion and transport
We compared DNA CpG methylation patterns in normal brain tissues and isocitrate dehydrogenase (IDH)-wild-type GBM specimens at initial diagnosis (GBM1) and at first recurrence (GBM2)
Summary
Zoltan Kraboth and Bence Galik co-authors contributed to the paper. Szentagothai Research Center, University of Pecs, 20. Glioblastoma (GBM) is the most aggressive brain tumor exhibiting great variability at histopathological and molecular levels. Its development is related to the accumulation of somatic genomic rearrangements, mutations and copy number alterations (CNAs), accompanied by changes in epigenomic and gene expression profiles. Chromothripsis, a sudden catastrophic rearrangement involving one or a few chromosomes, may play a role (Furgason et al 2015). Numerous studies presented genomic and transcriptomic characteristics of GBM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
