The DNA methylation landscape of primary triple-negative breast cancer
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 i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58158-x |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mattias Aine |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-133665e947724edcbdf4476df7db8c86 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-133665e947724edcbdf4476df7db8c862025-08-20T03:41:14ZengNature PortfolioNature Communications2041-17232025-03-0116112310.1038/s41467-025-58158-xThe DNA methylation landscape of primary triple-negative breast cancerMattias Aine0Deborah F. Nacer1Elsa Arbajian2Srinivas Veerla3Anna Karlsson4Jari Häkkinen5Henrik J. Johansson6Frida Rosengren7Johan Vallon-Christersson8Åke Borg9Johan Staaf10Division of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDepartment of Oncology-Pathology, Science for Life Laboratory, Karolinska InstitutetDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageDivision of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon VillageAbstract 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.https://doi.org/10.1038/s41467-025-58158-x |
| spellingShingle | 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 The DNA methylation landscape of primary triple-negative breast cancer Nature Communications |
| title | The DNA methylation landscape of primary triple-negative breast cancer |
| title_full | The DNA methylation landscape of primary triple-negative breast cancer |
| title_fullStr | The DNA methylation landscape of primary triple-negative breast cancer |
| title_full_unstemmed | The DNA methylation landscape of primary triple-negative breast cancer |
| title_short | The DNA methylation landscape of primary triple-negative breast cancer |
| title_sort | dna methylation landscape of primary triple negative breast cancer |
| url | https://doi.org/10.1038/s41467-025-58158-x |
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