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The DNA methylation landscape of primary triple-negative breast cancer

Aine, Mattias LU ; Nacer, Deborah F LU orcid ; Arbajian, Elsa LU ; Veerla, Srinivas LU orcid ; Karlsson, Anna LU ; Häkkinen, Jari LU orcid ; Johansson, Henrik J ; Rosengren, Frida LU ; Vallon-Christersson, Johan LU orcid and Borg, Åke LU , et al. (2025) In Nature Communications 16. p.1-23
Abstract

Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcriptional patterns are correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Further subdivision of the Basal and non-Basal subtypes identifies subgroups transcending genetic and proposed TNBC mRNA subtypes, demonstrating widely differing... (More)

Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcriptional patterns are correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Further subdivision of the Basal and non-Basal subtypes identifies subgroups transcending genetic and proposed TNBC mRNA subtypes, demonstrating widely differing immunological microenvironments, putative epigenetically-mediated immune evasion strategies, and a specific metabolic gene network in older patients that may be epigenetically regulated. Our study attempts to target the epigenetic backbone of TNBC, an approach that may inform future studies regarding tumor origins and the role of the microenvironment in shaping the cancer epigenome.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, DNA Methylation/genetics, Triple Negative Breast Neoplasms/genetics, Female, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, CpG Islands/genetics, Tumor Microenvironment/genetics, Middle Aged, Aged, Epigenome, Adult
in
Nature Communications
volume
16
article number
3041
pages
1 - 23
publisher
Nature Publishing Group
external identifiers
  • pmid:40155623
ISSN
2041-1723
DOI
10.1038/s41467-025-58158-x
language
English
LU publication?
yes
additional info
© 2025. The Author(s).
id
ce1e1d06-7a4a-446f-9685-c91e3a218bcd
date added to LUP
2025-04-01 23:08:11
date last changed
2025-04-04 14:51:55
@article{ce1e1d06-7a4a-446f-9685-c91e3a218bcd,
  abstract     = {{<p>Triple-negative breast cancer (TNBC) is a clinically challenging and molecularly heterogenous breast cancer subgroup. Here, we investigate the DNA methylation landscape of TNBC. By analyzing tumor methylome profiles and accounting for the genomic context of CpG methylation, we divide TNBC into two epigenetic subtypes corresponding to a Basal and a non-Basal group, in which characteristic transcriptional patterns are correlated with DNA methylation of distal regulatory elements and epigenetic regulation of key steroid response genes and developmental transcription factors. Further subdivision of the Basal and non-Basal subtypes identifies subgroups transcending genetic and proposed TNBC mRNA subtypes, demonstrating widely differing immunological microenvironments, putative epigenetically-mediated immune evasion strategies, and a specific metabolic gene network in older patients that may be epigenetically regulated. Our study attempts to target the epigenetic backbone of TNBC, an approach that may inform future studies regarding tumor origins and the role of the microenvironment in shaping the cancer epigenome.</p>}},
  author       = {{Aine, Mattias and Nacer, Deborah F and Arbajian, Elsa and Veerla, Srinivas and Karlsson, Anna and Häkkinen, Jari and Johansson, Henrik J and Rosengren, Frida and Vallon-Christersson, Johan and Borg, Åke and Staaf, Johan}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; DNA Methylation/genetics; Triple Negative Breast Neoplasms/genetics; Female; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; CpG Islands/genetics; Tumor Microenvironment/genetics; Middle Aged; Aged; Epigenome; Adult}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{1--23}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The DNA methylation landscape of primary triple-negative breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-58158-x}},
  doi          = {{10.1038/s41467-025-58158-x}},
  volume       = {{16}},
  year         = {{2025}},
}