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Cancers
Special Issues
Intratumoral Heterogeneity in Brain Cancers
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Intratumoral Heterogeneity in Brain Cancers

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 911

Special Issue Editor

Dr. Michael Oldham

E-Mail Website
Guest Editor
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA
Interests: adult malignant gliomas; human brain transcriptomics; gene coexpression meta-analysis; tumor vasculature; human brain evolution; metascience; scholarly communication

Special Issue Information

Dear Colleagues,

Brain tumors are complex ecosystems containing a significant number of malignant and nonmalignant cells. Clarifying the extent of intratumoral heterogeneity (ITH) in brain tumors is an important goal as ITH provides fuel for acquired resistance to targeted therapies. To achieve this, new strategies are needed to precisely identify distinct populations of malignant and nonmalignant cells in brain tumors, along with their defining molecular features.

We are pleased to invite submissions to this Special Issue on the topic of intratumoral heterogeneity in brain cancers. This Special Issue aims to collect a representative sample of cutting-edge experimental and computational strategies for analyzing ITH in different types of brain cancer. Review articles on the topic of ITH in brain cancers are also welcome. Themes of particular interest include clonal evolution, the tumor microenvironment, and multiomics/multiscale integration.

Dr. Michael Oldham
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

  • intratumoral heterogeneity
  • brain
  • clonal evolution
  • tumor microenvironment
  • multiomics

Published Papers (1 paper)

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Research

37 pages, 9293 KiB  
Article
Deconstructing Intratumoral Heterogeneity through Multiomic and Multiscale Analysis of Serial Sections
by Patrick G. Schupp, Samuel J. Shelton, Daniel J. Brody, Rebecca Eliscu, Brett E. Johnson, Tali Mazor, Kevin W. Kelley, Matthew B. Potts, Michael W. McDermott, Eric J. Huang, Daniel A. Lim, Russell O. Pieper, Mitchel S. Berger, Joseph F. Costello, Joanna J. Phillips and Michael C. Oldham
Cancers 2024, 16(13), 2429; https://doi.org/10.3390/cancers16132429 - 1 Jul 2024
Viewed by 762
Abstract
Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. [...] Read more.
Tumors may contain billions of cells, including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that are consistently expressed by astrocytoma truncal clones, including AKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors. Full article
(This article belongs to the Special Issue Intratumoral Heterogeneity in Brain Cancers)
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