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Genome-Wide DNA Methylation Profiling of Triple-Negative Breast Cancer Uncovers Epigenetic Biomarkers of Tumor Identity and the Immune Microenvironment

Sasiain Casado, Inaki LU orcid ; Nacer, Deborah F. LU orcid ; Jönsson, Mats LU ; Vallon-Christersson, Johan LU orcid ; Grigoriadis, Anita ; Aine, Mattias LU and Staaf, Johan LU orcid (2026) In npj Breast Cancer 12(1). p.1-20
Abstract
DNA methylation deregulation is an essential feature of tumor biology, influencing cancer formation and pathogenesis. Analyses of DNA methylation in bulk cancer specimens are challenging due to the high data dimensionality, noise, and mixture of different cell types. Here, we characterized methylation dynamics in cancer by investigating the variance structure of bulk tumor DNA methylation data through the identification of groups of highly correlated CpGs, termed CpG cassettes. Using triple-negative breast cancer as a model system, our approach identified co-occurring methylation patterns linked to different intrinsic tumor processes and pathways, gene inactivation, and composition of the tumor immune microenvironment. Our framework also... (More)
DNA methylation deregulation is an essential feature of tumor biology, influencing cancer formation and pathogenesis. Analyses of DNA methylation in bulk cancer specimens are challenging due to the high data dimensionality, noise, and mixture of different cell types. Here, we characterized methylation dynamics in cancer by investigating the variance structure of bulk tumor DNA methylation data through the identification of groups of highly correlated CpGs, termed CpG cassettes. Using triple-negative breast cancer as a model system, our approach identified co-occurring methylation patterns linked to different intrinsic tumor processes and pathways, gene inactivation, and composition of the tumor immune microenvironment. Our framework also demonstrated the presence of high-variance DNA methylation, seemingly not linked to tumor biology, that could be excluded using chromatin accessibility filtering. Together, this work outlines a comprehensive approach to analyze bulk tumor DNA methylation data, combining tumor purity adjustment, functional CpG filtering, stratification by CpG contexts, and identification of highly correlated CpG modules to enhance tumor-intrinsic DNA methylation patterns and our understanding of processes shaping epigenetic tumor evolution. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
npj Breast Cancer
volume
12
issue
1
article number
105
pages
1 - 20
publisher
Nature Publishing Group
external identifiers
  • pmid:42586974
  • scopus:105047398855
ISSN
2374-4677
DOI
10.1038/s41523-026-01030-y
language
English
LU publication?
yes
id
10f7e203-651b-4f9d-88c9-9ab9611a7805
date added to LUP
2026-08-31 15:08:57
date last changed
2026-09-01 04:01:01
@article{10f7e203-651b-4f9d-88c9-9ab9611a7805,
  abstract     = {{DNA methylation deregulation is an essential feature of tumor biology, influencing cancer formation and pathogenesis. Analyses of DNA methylation in bulk cancer specimens are challenging due to the high data dimensionality, noise, and mixture of different cell types. Here, we characterized methylation dynamics in cancer by investigating the variance structure of bulk tumor DNA methylation data through the identification of groups of highly correlated CpGs, termed CpG cassettes. Using triple-negative breast cancer as a model system, our approach identified co-occurring methylation patterns linked to different intrinsic tumor processes and pathways, gene inactivation, and composition of the tumor immune microenvironment. Our framework also demonstrated the presence of high-variance DNA methylation, seemingly not linked to tumor biology, that could be excluded using chromatin accessibility filtering. Together, this work outlines a comprehensive approach to analyze bulk tumor DNA methylation data, combining tumor purity adjustment, functional CpG filtering, stratification by CpG contexts, and identification of highly correlated CpG modules to enhance tumor-intrinsic DNA methylation patterns and our understanding of processes shaping epigenetic tumor evolution.}},
  author       = {{Sasiain Casado, Inaki and Nacer, Deborah F. and Jönsson, Mats and Vallon-Christersson, Johan and Grigoriadis, Anita and Aine, Mattias and Staaf, Johan}},
  issn         = {{2374-4677}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  pages        = {{1--20}},
  publisher    = {{Nature Publishing Group}},
  series       = {{npj Breast Cancer}},
  title        = {{Genome-Wide DNA Methylation Profiling of Triple-Negative Breast Cancer Uncovers Epigenetic Biomarkers of Tumor Identity and the Immune Microenvironment}},
  url          = {{http://dx.doi.org/10.1038/s41523-026-01030-y}},
  doi          = {{10.1038/s41523-026-01030-y}},
  volume       = {{12}},
  year         = {{2026}},
}