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Cancers
Special Issues
Pathology and Genetics of Glioblastoma
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Pathology and Genetics of Glioblastoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 1514

Special Issue Editor

Dr. Theo Kraus

E-Mail Website
Guest Editor
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstraße 48, A-5020 Salzburg, Austria
Interests: meningiomas; glioma; glioblastoma; ganglioglioma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastomas (GBMs) are the most common primary brain tumors of adults. They show aggressive behavior and a poor prognosis, and despite intensive research on molecular targets, there is still no curative therapy. In the current 2021 WHO Classification of CNS tumors, novel genetic and epigenetic aspects are highlighted, contributing to GBM initiation and progression.

The most common genetic alterations in GBMs are TERT mutations as well as EGFR amplifications and CDKN2A/B deletions. Furthermore, GBMs show aberrant DNA-methylation landscapes altering numerous biological pathways. This leads to an intimate relationship of GBM cells with the microenvironment, supporting tumor growth. Therefore, it is necessary to understand genetic and epigenetic mechanisms occurring in GBMs in order develop advanced therapy strategies.

This Special Issue of Cancers invites contributions (original research articles and reviews) that highlight our enhanced understanding of the genomic and epigenomic landscape of GBMs to better understand the pathology underlying glioblastomas, opening up new ways in glioblastoma therapy. 

We look forward to receiving your contributions.

Dr. Theo Kraus
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma
  • pathology
  • genetics
  • genomics
  • epigenomics

Published Papers (1 paper)

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Research

11 pages, 6548 KiB  
Article
Dissecting the Methylomes of EGFR-Amplified Glioblastoma Reveals Altered DNA Replication and Packaging, and Chromatin and Gene Silencing Pathways
by Theo F. J. Kraus, Celina K. Langwieder, Dorothee Hölzl, Georg Hutarew, Hans U. Schlicker, Beate Alinger-Scharinger, Christoph Schwartz and Karl Sotlar
Cancers 2023, 15(13), 3525; https://doi.org/10.3390/cancers15133525 - 7 Jul 2023
Cited by 1 | Viewed by 1246
Abstract
Glioblastoma IDH wildtype is the most frequent brain tumor in adults. It shows a highly malignant behavior and devastating outcomes. To date, there is still no targeted therapy available; thus, patients’ median survival is limited to 12–15 months. Epithelial growth factor receptor ( [...] Read more.
Glioblastoma IDH wildtype is the most frequent brain tumor in adults. It shows a highly malignant behavior and devastating outcomes. To date, there is still no targeted therapy available; thus, patients’ median survival is limited to 12–15 months. Epithelial growth factor receptor (EGFR) is an interesting targetable candidate in advanced precision medicine for brain tumor patients. In this study, we performed integrated epigenome-wide DNA-methylation profiling of 866,895 methylation specific sites in 50 glioblastoma IDH wildtype samples, comparing EGFR amplified and non-amplified glioblastomas. We found 9849 significantly differentially methylated CpGs (DMCGs) with Δβ ≥ 0.1 and p-value < 0.05 in EGFR amplified, compared to EGFR non-amplified glioblastomas. Of these DMCGs, 2380 were annotated with tiling (2090), promoter (117), gene (69) and CpG islands (104); 7460 are located at other loci. Interestingly, the list of differentially methylated genes allocated eleven functionally relevant RNAs: five miRNAs (miR1180, miR1255B1, miR126, miR128-2, miR3125), two long non-coding RNAs (LINC00474, LINC01091), and four antisense RNAs (EPN2-AS1, MNX1-AS2, NKX2-2-AS1, WWTR1-AS1). Gene ontology (GO) analysis showed enrichment of “DNA replication-dependent nucleosome assembly”, “chromatin silencing at rDNA”, “regulation of gene silencing by miRNA”, “DNA packaging”, “posttranscriptional gene silencing”, “gene silencing by RNA”, “negative regulation of gene expression, epigenetic”, “regulation of gene silencing”, “protein-DNA complex subunit organization”, and “DNA replication-independent nucleosome organization” pathways being hypomethylated in EGFR amplified glioblastomas. In summary, dissecting the methylomes of EGFR amplified and non-amplified glioblastomas revealed altered DNA replication, DNA packaging, chromatin silencing and gene silencing pathways, opening potential novel targets for future precision medicine. Full article
(This article belongs to the Special Issue Pathology and Genetics of Glioblastoma)
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