The DNA methylation landscape of primary triple-negative breast cancer

Mattias Aine, Deborah F. Nacer, Elsa Arbajian, Srinivas Veerla, Anna Karlsson, Jari Häkkinen, Henrik J. Johansson, Frida Rosengren, Johan Vallon-Christersson, Åke Borg and Johan Staaf ()
Additional contact information
Mattias Aine: Medicon Village
Deborah F. Nacer: Medicon Village
Elsa Arbajian: Medicon Village
Srinivas Veerla: Medicon Village
Anna Karlsson: Medicon Village
Jari Häkkinen: Medicon Village
Henrik J. Johansson: Karolinska Institutet
Frida Rosengren: Medicon Village
Johan Vallon-Christersson: Medicon Village
Åke Borg: Medicon Village
Johan Staaf: Medicon Village

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: 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 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58158-x

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DOI: 10.1038/s41467-025-58158-x

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