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The DNA methylation landscape of primary triple-negative breast cancer

Author

Listed:
  • Mattias Aine

    (Medicon Village)

  • Deborah F. Nacer

    (Medicon Village
    Medicon Village)

  • Elsa Arbajian

    (Medicon Village)

  • Srinivas Veerla

    (Medicon Village
    Medicon Village)

  • Anna Karlsson

    (Medicon Village
    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
    Medicon Village)

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.

Suggested Citation

  • Mattias Aine & Deborah F. Nacer & Elsa Arbajian & Srinivas Veerla & Anna Karlsson & Jari Häkkinen & Henrik J. Johansson & Frida Rosengren & Johan Vallon-Christersson & Åke Borg & Johan Staaf, 2025. "The DNA methylation landscape of primary triple-negative breast cancer," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58158-x
    DOI: 10.1038/s41467-025-58158-x
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    References listed on IDEAS

    as
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