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Cancers
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Heterogeneity in Intra-Cranial Tumors: Diagnostic, Prognostic, and Therapeutic Implications
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Heterogeneity in Intra-Cranial Tumors: Diagnostic, Prognostic, and Therapeutic Implications

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

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 4358

Special Issue Editors

Prof. Dr. Francois Ducray

E-Mail Website
Guest Editor
Department of Neuro-Oncology, Hospices Civils de Lyon, Bron, France
Interests: gliomas; glioblastoma stem cells; targeted therapies; tumor heterogeneity
Special Issues, Collections and Topics in MDPI journals
Dr. Shawn L. Hervey-Jumper

E-Mail Website
Guest Editor
Department of Neurological Surgery, University of California, San Francisco, CA, USA
Interests: cancer neurosciences; gliomas; functional network interactions; specific brain mapping strategies
Dr. Thiebaud Picart

E-Mail Website
Guest Editor
Department of Neurosurgery, Hospices Civils de Lyon, Bron, France
Interests: fluorescence-guided surgery; gliomas; glioblastoma stem cells; tumor intrinsic connectivity; tumor heterogeneity

Special Issue Information

Dear Colleagues,

Recent advances have been made in diagnosing intra-cranial tumors, with a better definition of inter-tumoral heterogeneity. For instance, the WHO introduced a histo-molecular classification of gliomas in 2016, and new tumor entities, such as high-grade gliomas with piloid features, have been described. Additionally, there is also a high degree of intra-tumoral heterogeneity. Multiple tumor sampling and tumor resampling at progression have deciphered this heterogeneity at the spatial and temporal levels. From a functional viewpoint, the coexistence of areas characterized by different degrees of intrinsic connectivity has been demonstrated in gliomas. Moreover, single-cell analysis, notably applied to gliomas, has offered a better overview of inter- and intra-tumoral heterogeneity, identifying different transcriptomic signatures within the same tumor. This Special Issue aims to provide updated data regarding the inter- and intra-tumoral heterogeneity of intracranial neoplasms (gliomas, meningiomas, metastasis, etc.) and determine how this heterogeneity will influence therapeutic strategies and outcomes.

Prof. Dr. Francois Ducray
Dr. Shawn L. Hervey-Jumper
Dr. Thiebaud Picart
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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

  • glioma
  • histo-molecular classification
  • intra-tumoral heterogeneity
  • inter-tumoral heterogeneity
  • meningioma
  • neuro-oncology
  • neurosurgery

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Published Papers (3 papers)

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Research

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24 pages, 3500 KB  
Article
Chromosome 1p and 6q Loss of Heterozygosity in Meningioma: A Comprehensive Analysis of the Two Chromatin Remodeling Complex Subunits ARID1A and ARID1B
by Manuel Hinsberger, Julia Becker-Kettern, Wiebke M. Jürgens-Wemheuer, Katrin Bartelmei, Ralf Ketter, Joachim Oertel and Walter J. Schulz-Schaeffer
Cancers 2026, 18(9), 1325; https://doi.org/10.3390/cancers18091325 - 22 Apr 2026
Viewed by 420
Abstract
Background/Objectives: Loss of heterozygosity (LOH) in meningioma has been known for more than two decades. It has been shown that LOH on chromosome 1p36 is an independent marker of meningioma recurrence and progression. ARID1A, a tumor suppressor gene located on chromosome [...] Read more.
Background/Objectives: Loss of heterozygosity (LOH) in meningioma has been known for more than two decades. It has been shown that LOH on chromosome 1p36 is an independent marker of meningioma recurrence and progression. ARID1A, a tumor suppressor gene located on chromosome 1p36.11, is part of the chromatin-regulating SWI/SNF complex whose subunits are altered in 20% of cases across all tumor entities. Methods: Using our newly developed indirect enzyme-linked immunosorbent assay (ELISA), we investigated whether tumors with or without LOH 1p differ in ARID1A expression in 61 meningiomas. To study possible links between ARID1A and ARID1B, we tested for LOH 6q in association with LOH 1p using a PCR-based microsatellite approach. ARID1B, another member of the SWI/SNF complex, is located on 6q25.3. Additionally, we compared our ELISA results with immunohistochemistry data staining of ARID1A in tissue sections known to harbor LOH 1p. Results: Our results indicate that meningiomas harboring LOH 1p have significantly lower ARID1A levels compared to tumors without LOH 1p. In free nuclear protein fractions, reductions were up to 32% (CI: 6–58.7%). Interestingly, we found that ARID1A levels were significantly lower in tumors with recurrence and/or multiple localizations. In addition, our analysis of chromosome 6q uncovered a significantly strong correlation between LOH 1p and LOH 6q (p < 0.0001). Conclusions: These results highlight the importance of ARID1A in meningioma malignization and indicate for the first time functional evidence for LOH 1p. Full article
(This article belongs to the Special Issue Heterogeneity in Intra-Cranial Tumors: Diagnostic, Prognostic, and Therapeutic Implications)
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Review

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10 pages, 750 KB  
Review
Histo-Molecular Intratumoral Heterogeneity in Meningiomas: A Narrative Review
by Nourou Dine Adeniran Bankole, Tuan Le Van, Luc Kerherve, Edouard Morlaix, Jean-François Bellus, Kerima Belhajali, Julian Lopez, Pierre De Buck, Alia Sayda Houidi, Walid Farah, Maxime Lleu, Olivier Baland, Cathy Cao, Ahmed El Cadhi, Jacques Beaurain, Thiebaud Picart and Moncef Berhouma
Cancers 2026, 18(8), 1206; https://doi.org/10.3390/cancers18081206 - 10 Apr 2026
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Abstract
Background: Meningiomas, the most common primary intracranial tumors, are predominantly benign, but high-grade variants show marked aggressiveness, histo-molecular heterogeneity, and treatment resistance. Although the 2021 WHO CNS classification integrates molecular and histopathologic criteria, substantial inter- and intratumoral variability still limits prognostic accuracy [...] Read more.
Background: Meningiomas, the most common primary intracranial tumors, are predominantly benign, but high-grade variants show marked aggressiveness, histo-molecular heterogeneity, and treatment resistance. Although the 2021 WHO CNS classification integrates molecular and histopathologic criteria, substantial inter- and intratumoral variability still limits prognostic accuracy and treatment effectiveness. The goal was to provide insight regarding the histo-molecular intratumoral heterogeneity (ITH) of meningioma and examine its clinical implications. Methods: A narrative review was performed in accordance with PRISMA guidelines. PubMed and Google Scholar were screened for studies on “meningioma” and “intratumoral heterogeneity” published up to 28 July 2025. Eligible studies included original human research reporting histological or molecular heterogeneity with clinical relevance. Results: Eighteen studies comprising 2952 meningioma patients (mean age 59.4 ± 14.8 years, range 16–85) were included. Integrated cytogenetic, molecular, and spatial analyses, including FISH, karyotyping, scRNA-seq, CNV profiling, and spatial transcriptomics, revealed multilayered histo-molecular heterogeneity. Histologically, regional variations in morphology and proliferative index increased with tumor grade. Genomic diversity, marked by recurrent losses of 1p, 14q, and 22q and transcriptionally distinct subclones, defined a complex tumor architecture. Spatial and temporal analyses demonstrated subclonal expansion, stepwise clonal evolution, and therapy resistance, particularly in recurrent tumors. Functionally, SULT1E1+ subclones and COL6A3-mediated macrophage–tumor interactions emerged as potential key drivers of malignancy, recurrence, and radioresistance. Conclusions: Histo-molecular diversity underlies meningioma progression, recurrence, and therapeutic resistance. Standardization of ITH assessment, integration of AI-based spatial analytics, and the development of subclone-specific therapies are essential next steps toward advancing precision neuro-oncology. Full article
(This article belongs to the Special Issue Heterogeneity in Intra-Cranial Tumors: Diagnostic, Prognostic, and Therapeutic Implications)
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Other

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14 pages, 1141 KB  
Systematic Review
Adult Cerebellopontine Angle Medulloblastoma: A Systematic Review of Clinical Features, Management Approaches, and Patient Outcomes
by Kishore Balasubramanian, Abdurrahman F. Kharbat, Francisco Call-Orellana, Sherwin A. Tavakol, Grace R. Fassina, Christopher Janssen, Othman Bin Alamer, Jeffrey A. Zuccato and Ian F. Dunn
Cancers 2024, 16(24), 4242; https://doi.org/10.3390/cancers16244242 - 20 Dec 2024
Cited by 1 | Viewed by 2487
Abstract
Objective: The aim of this study was to systematically review the existing individual patient data in the literature on adult cerebellopontine angle (CPA) medulloblastoma (MB) and characterize the patient presentation, management strategies used, and oncological outcomes of this rare entity to guide future [...] Read more.
Objective: The aim of this study was to systematically review the existing individual patient data in the literature on adult cerebellopontine angle (CPA) medulloblastoma (MB) and characterize the patient presentation, management strategies used, and oncological outcomes of this rare entity to guide future clinical practice. Methods: Following PRISMA guidelines, a systematic review was conducted by searching PubMed, EMBASE, Web of Science, and Cochrane databases from inception to 19 June 2024. Studies regarding adult patients with histologically confirmed MB radiographically confirmed to be located in the CPA were included. Clinical data were synthesized, and predictors of outcomes were evaluated. Results: Twenty-seven studies with 42 adult CPAMB patients were included. The median age was 32 years (range: 19–56). Headaches (81%), cranial neuropathy (90%), cerebellar dysfunction (79%), and nausea/vomiting (50%) were typical presenting features. The predominant histological subtype was the classic variant. Maximal safe surgical resection was performed, most commonly using a retrosigmoid approach, and 60% of cases received a gross total resection. Most patients received adjuvant treatment (93%), typically chemoradiotherapy. The recurrence rate was 11% after a median of 18 months of follow-up. Relatively high survival rates of 96%, 85%, and 85% were observed at 1, 3, and 5 years, respectively. Patients who received adjuvant therapy had significantly better recurrence and greater overall survival outcomes. Conclusions: These results support the consideration of MB in young adult patients presenting with CPA tumors with radiographical features suggestive of hypercellularity and the utilization of a management strategy of maximal safe resection plus post-operative craniospinal irradiation along with chemotherapy to optimally treat these rare patients. Full article
(This article belongs to the Special Issue Heterogeneity in Intra-Cranial Tumors: Diagnostic, Prognostic, and Therapeutic Implications)
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