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Cancers
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Central Nervous System Tumors—the 2021 WHO Classification and Beyond
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Central Nervous System Tumors—the 2021 WHO Classification and Beyond

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 15597

Special Issue Editor

Dr. Audrey Rousseau

E-Mail Website
Guest Editor
Département de Pathologie Cellulaire et Tissulaire, CHU Angers, 4 rue Larrey, 49933 Angers, CEDEX 9, France
Interests: central nervous system tumors; gliomas; neuropathology; genetics; neuro-oncology

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue of Cancers entitled “Central Nervous System Tumors—The 2021 WHO Classification and Beyond”.

In this Special Issue, original research articles, opinion papers, and reviews are welcome. Topics may include (but are not limited to) the following:

  • The new entities of the 2021 WHO classification of CNS tumors;
  • The taxonomy of adult- and pediatric-type diffuse gliomas;
  • The taxonomy of ependymomas;
  • CNS embryonal tumors other than medulloblastomas;
  • The future of methylation profiling in CNS tumor diagnostics;
  • Targeted therapies in primary CNS tumors;
  • Immunotherapy in primary CNS tumors;
  • The microenvironment in diffuse gliomas.

We look forward to receiving your contributions.

Dr. Audrey Rousseau
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 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

  • 2021 WHO classification
  • diffuse gliomas
  • CNS embryonal tumors
  • ependymomas
  • genetics
  • epigenetics
  • methylation profiling
  • targeted therapy
  • immunotherapy
  • tumor microenvironment

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Published Papers (6 papers)

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Research

Jump to: Review

13 pages, 8229 KiB  
Article
Midline Gliomas: A Retrospective Study from a Cancer Center in the Middle East
by Sarah Al Sharie, Dima Abu Laban, Jamil Nazzal, Shahad Iqneibi, Sura Ghnaimat, Abdallah Al-Ani and Maysa Al-Hussaini
Cancers 2023, 15(18), 4545; https://doi.org/10.3390/cancers15184545 - 13 Sep 2023
Cited by 1 | Viewed by 1395
Abstract
Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) [...] Read more.
Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) is a diffuse glioma that occurs in the classical midline structures, characterized by a specific genetic alteration, and associated with grim outcome. This study was conducted at King Hussein Cancer Center and reviewed the medical records of 104 patients with circumscribed and diffuse gliomas involving midline structures that underwent biopsy between 2005 and 2022. We included a final cohort of 104 patients characterized by a median age of 23 years and a male-to-female ratio of 1.59-to-1. Diffuse high-grade glioma (DHGG) was the most common pathological variant (41.4%), followed by DMG (28.9%). GFAP was positive in most cases (71.2%). Common positive mutations/alterations detected by surrogate immunostains included H3 K27me3 (28.9%), p53 (25.0%), and H3 K27M (20.2%). Age group, type of treatment, and immunohistochemistry were significantly associated with both the location of the tumor and tumor variant (all; p < 0.05). DMGs were predominantly found in the thalamus, whereas circumscribed gliomas were most commonly observed in the spinal cord. None of the diffuse gliomas outside the classical location, or circumscribed gliomas harbored the defining DMG mutations. The median overall survival (OS) for the entire cohort was 10.6 months. Only the tumor variant (i.e., circumscribed gliomas) and radiotherapy were independent prognosticators on multivariate analysis. Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
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21 pages, 5374 KiB  
Article
Mitochondrial Peptide Humanin Facilitates Chemoresistance in Glioblastoma Cells
by Jorge A. Peña Agudelo, Matías L. Pidre, Matias Garcia Fallit, Melanie Pérez Küper, Camila Zuccato, Alejandro J. Nicola Candia, Abril Marchesini, Mariana B. Vera, Emilio De Simone, Carla Giampaoli, Leslie C. Amorós Morales, Nazareno Gonzalez, Víctor Romanowski, Guillermo A. Videla-Richardson, Adriana Seilicovich and Marianela Candolfi
Cancers 2023, 15(16), 4061; https://doi.org/10.3390/cancers15164061 - 11 Aug 2023
Cited by 6 | Viewed by 2721
Abstract
Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects [...] Read more.
Humanin (HN) is a mitochondrial-derived peptide with robust cytoprotective effects in many cell types. Although the administration of HN analogs has been proposed to treat degenerative diseases, its role in the pathogenesis of cancer is poorly understood. Here, we evaluated whether HN affects the chemosensitivity of glioblastoma (GBM) cells. We found that chemotherapy upregulated HN expression in GBM cell lines and primary cultures derived from GBM biopsies. An HN analog (HNGF6A) boosted chemoresistance, increased the migration of GBM cells and improved their capacity to induce endothelial cell migration and proliferation. Chemotherapy also upregulated FPR2 expression, an HN membrane-bound receptor, and the HNGF6A cytoprotective effects were inhibited by an FPR2 receptor antagonist (WRW4). These effects were observed in glioma cells with heterogeneous genetic backgrounds, i.e., glioma cells with wild-type (wtIDH) and mutated (mIDH) isocitrate dehydrogenase. HN silencing using a baculoviral vector that encodes for a specific shRNA for HN (BV.shHN) reduced chemoresistance, and impaired the migration and proangiogenic capacity of GBM cells. Taken together, our findings suggest that HN boosts the hallmark characteristics of GBM, i.e., chemoresistance, migration and endothelial cell proliferation. Thus, strategies that inhibit the HN/FPR2 pathway may improve the response of GBM to standard therapy Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
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11 pages, 1157 KiB  
Article
Frequency and Prognostic Relevance of Volumetric MRI Changes in Contrast- and Non-Contrast-Enhancing Tumor Compartments between Surgery and Radiotherapy of IDHwt Glioblastoma
by Nico Teske, Nina C. Teske, Maximilian Niyazi, Claus Belka, Niklas Thon, Joerg-Christian Tonn, Robert Forbrig and Philipp Karschnia
Cancers 2023, 15(6), 1745; https://doi.org/10.3390/cancers15061745 - 14 Mar 2023
Cited by 3 | Viewed by 1583
Abstract
In newly diagnosed IDH-wildtype glioblastoma, the frequency and prognostic relevance of tumor regrowth between resection and the initiation of adjuvant radiochemotherapy are unclear. In this retrospective single-center study we included 64 consecutive cases, for whom magnetic resonance imaging (MRI) was available for both [...] Read more.
In newly diagnosed IDH-wildtype glioblastoma, the frequency and prognostic relevance of tumor regrowth between resection and the initiation of adjuvant radiochemotherapy are unclear. In this retrospective single-center study we included 64 consecutive cases, for whom magnetic resonance imaging (MRI) was available for both the volumetric assessment of the extent of resection immediately after surgery as well as the volumetric target delineation before the initiation of adjuvant radiochemotherapy (time interval: 15.5 ± 1.9 days). Overall, a median new contrast-enhancement volume was seen in 21/64 individuals (33%, 1.5 ± 1.5 cm3), and new non-contrast lesion volume in 18/64 patients (28%, 5.0 ± 2.3 cm3). A multidisciplinary in-depth review revealed that new contrast-enhancement was either due to (I) the progression of contrast-enhancing tumor remnants in 6/21 patients or (II) distant contrast-enhancing foci or breakdown of the blood–brain barrier in previously non-contrast-enhancing tumor remnants in 5/21 patients, whereas it was unspecific or due to ischemia in 10/21 patients. For non-contrast-enhancing lesions, three of eighteen had progression of non-contrast-enhancing tumor remnants and fifteen of eighteen had unspecific changes or changes due to ischemia. There was no significant association between findings consistent with tumor regrowth and a less favorable outcome (overall survival: 14 vs. 19 months; p = 0.423). These findings support the rationale that analysis of the postsurgical remaining tumor-volume for prognostic stratification should be carried out on immediate postoperative MRI (<72 h), as unspecific changes are common. However, tumor regrowth including distant foci may occur in a subset of IDH-wildtype glioblastoma patients diagnosed per WHO 2021 classification. Thus, MRI imaging prior to radiotherapy should be obtained to adjust radiotherapy planning accordingly. Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
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Review

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25 pages, 5227 KiB  
Review
Decoding Diffuse Midline Gliomas: A Comprehensive Review of Pathogenesis, Diagnosis and Treatment
by Sarah Al Sharie, Dima Abu Laban and Maysa Al-Hussaini
Cancers 2023, 15(19), 4869; https://doi.org/10.3390/cancers15194869 - 6 Oct 2023
Cited by 5 | Viewed by 3135
Abstract
Diffuse midline gliomas (DMGs) are a group of aggressive CNS tumors, primarily affecting children and young adults, which have historically been associated with dismal outcomes. As the name implies, they arise in midline structures in the CNS, primarily in the thalamus, brainstem, and [...] Read more.
Diffuse midline gliomas (DMGs) are a group of aggressive CNS tumors, primarily affecting children and young adults, which have historically been associated with dismal outcomes. As the name implies, they arise in midline structures in the CNS, primarily in the thalamus, brainstem, and spinal cord. In more recent years, significant advances have been made in our understanding of DMGs, including molecular features, with the identification of potential therapeutic targets. We aim to provide an overview of the most recent updates in the field of DMGs, including classification, molecular subtypes, diagnostic techniques, and emerging therapeutic strategies including a review of the ongoing clinical trials, thus providing the treating multidisciplinary team with a comprehensive understanding of the current landscape and potential therapeutic strategies for this devastating group of tumors. Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
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27 pages, 426 KiB  
Review
Epigenetic Regulation in Primary CNS Tumors: An Opportunity to Bridge Old and New WHO Classifications
by Danielle D. Dang, Jared S. Rosenblum, Ashish H. Shah, Zhengping Zhuang and Tara T. Doucet-O’Hare
Cancers 2023, 15(9), 2511; https://doi.org/10.3390/cancers15092511 - 27 Apr 2023
Cited by 1 | Viewed by 2384
Abstract
Originally approved in 1979, a specific grading classification for central nervous system (CNS) tumors was devised by the World Health Organization (WHO) in an effort to guide cancer treatment and better understand prognosis. These “blue books” have since undergone several iterations based on [...] Read more.
Originally approved in 1979, a specific grading classification for central nervous system (CNS) tumors was devised by the World Health Organization (WHO) in an effort to guide cancer treatment and better understand prognosis. These “blue books” have since undergone several iterations based on tumor location, advancements in histopathology, and most recently, diagnostic molecular pathology in its fifth edition. As new research methods have evolved to elucidate complex molecular mechanisms of tumorigenesis, a need to update and integrate these findings into the WHO grading scheme has become apparent. Epigenetic tools represent an area of burgeoning interest that encompasses all non-Mendelian inherited genetic features affecting gene expression, including but not limited to chromatin remodeling complexes, DNA methylation, and histone regulating enzymes. The SWItch/Sucrose non-fermenting (SWI/SNF) chromatin remodeling complex is the largest mammalian family of chromatin remodeling proteins and is estimated to be altered in 20–25% of all human malignancies; however, the ways in which it contributes to tumorigenesis are not fully understood. We recently discovered that CNS tumors with SWI/SNF mutations have revealed an oncogenic role for endogenous retroviruses (ERVs), remnants of exogenous retroviruses that integrated into the germline and are inherited like Mendelian genes, several of which retain open reading frames for proteins whose expression putatively contributes to tumor formation. Herein, we analyzed the latest WHO classification scheme for all CNS tumors with documented SWI/SNF mutations and/or aberrant ERV expression, and we summarize this information to highlight potential research opportunities that could be integrated into the grading scheme to better delineate diagnostic criteria and therapeutic targets. Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
14 pages, 1129 KiB  
Review
PIEZO1-Related Physiological and Pathological Processes in CNS: Focus on the Gliomas
by Rui Hong, Dianxu Yang, Yao Jing, Shiwen Chen, Hengli Tian and Yang Yang
Cancers 2023, 15(3), 883; https://doi.org/10.3390/cancers15030883 - 31 Jan 2023
Cited by 3 | Viewed by 3699
Abstract
PIEZO1 is ubiquitously expressed in cells in different kinds of tissues throughout the body, which can sense physical or mechanical stimuli and translate them into intracellular electrochemical signals to regulate organism functions. In particular, PIEZO1 appears in complex interactive regulatory networks as a [...] Read more.
PIEZO1 is ubiquitously expressed in cells in different kinds of tissues throughout the body, which can sense physical or mechanical stimuli and translate them into intracellular electrochemical signals to regulate organism functions. In particular, PIEZO1 appears in complex interactive regulatory networks as a central node, governing normal and pathological functions in the body. However, the effect and mechanism of the activation or expression of PIEZO1 in diseases of the central nervous system (CNS) remain unclear. On one hand, in CNS diseases, pathophysiological processes in neurons and glial are often accompanied by variations in the mechanical properties of the cellular and extracellular matrix stiffness. The expression of PIEZO1 can therefore be upregulated, in responding to mechanical stimulation, to drive the biological process in cells, which in turns indirectly affects the cellular microenvironment, resulting in alterations of the cellular status. On the other hand, it may have contradictory effects with the change of active patterns and/or subcellular location. This review highlights the biological processes involved with PIEZO1 in CNS cells, with special emphasis on its multiple roles in glioma-associated phenotypes. In conclusion, PIEZO1 can be used as an indicator to assess the malignancy and prognosis of patients with gliomas, as well as a therapeutic target for clinical application following fully exploring the potential mechanism of PIEZO1 in CNS diseases. Full article
(This article belongs to the Special Issue Central Nervous System Tumors—the 2021 WHO Classification and Beyond)
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