Epigenome-Wide DNA Methylation Profiling of Matched Primary Breast Cancers and Brain Metastases Reveals Epigenetic Markers linked to Metastatic Progression: A Preliminary Study.
9 affiliations
- 1Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria.
- 2Department of Neurosurgery, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
- 3Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria.
- 4Department of Neurosurgery, München Klinik Bogenhausen, Munich, Germany.
- 5Division of Neuropathology, Neuromed Campus, Institute of Pathology and Molecular Pathology, Kepler University Hospital, Johannes Kepler University, Linz, Austria and Clinical Research Institute for Neurosciences, Johannes Kepler University Linz, Austria.
- 6Clinic of Internal Medicine 3, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
- 7Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Salzburg, Austria.
- 8Cancer Cluster Salzburg, Salzburg, Austria.
- 9Division of Oncology, Department for Internal Medicine, Medical University Graz, Graz, Austria.
Abstract
Introduction
Breast cancer represents the most prevalent malignancy among women globally, with a rising incidence of metastases to the central nervous system. The presence of brain metastases is associated with a poor prognosis, largely due to the limited availability of effective treatment modalities.Methods
In this preliminary study, we performed an epigenome-wide DNA-methylation analysis of matched primary breast cancer and brain metastasis of the same patients applying the Illumina Infinium EPIC Bead Chip interrogating more than 850,000 CpG sites at single base resolution.Results
We found that primary breast cancers and corresponding metastases are very similar on the global DNA methylation level. Detailed analysis showed aberrant methylation patterns that reflect the process of brain metastasis. We identified 107 nominally significant methylated CpG sites (DMCGs) within promoter and gene regions (Δβ ≥ 0.1, p-value < 0.05), when comparing primary breast tumors to their brain metastatic counterparts. However, due to the limited sample size, no individual CpG site retained statistically significant after correction for multiple testing.Conclusion
Our study highlights specific aberrant DNA methylation patterns that are associated with brain metastasis in breast cancer. Characterizing these epigenetic alterations provides a promising avenue for identifying novel therapeutic targets and clinically relevant biomarkers.
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BibTeX
@article{alingerscharinger2026epigenomewide,
title = {{Epigenome-Wide DNA Methylation Profiling of Matched Primary Breast Cancers and Brain Metastases Reveals Epigenetic Markers linked to Metastatic Progression: A Preliminary Study.}},
author = {Beate Alinger-Scharinger and Georg Hutarew and Christoph Schwartz and Alexander Romagna and Ognian Kalev and Serge Weis and Simon P Gampenrieder and Gabriel Rinnerthaler and Vanessa Castagnaviz and Franz Gassner and Roland Geisberger and Nadja Zaborsky and Richard Greil and Karl Sotlar and Theo F J Kraus},
journal = {International journal of medical sciences},
year = {2026},
month = oct,
doi = {10.7150/ijms.130407},
url = {https://europepmc.org/article/MED/42909893},
note = {CC BY},
}
RIS
TY - JOUR
TI - Epigenome-Wide DNA Methylation Profiling of Matched Primary Breast Cancers and Brain Metastases Reveals Epigenetic Markers linked to Metastatic Progression: A Preliminary Study.
AU - Beate Alinger-Scharinger
AU - Georg Hutarew
AU - Christoph Schwartz
AU - Alexander Romagna
AU - Ognian Kalev
AU - Serge Weis
AU - Simon P Gampenrieder
AU - Gabriel Rinnerthaler
AU - Vanessa Castagnaviz
AU - Franz Gassner
AU - Roland Geisberger
AU - Nadja Zaborsky
AU - Richard Greil
AU - Karl Sotlar
AU - Theo F J Kraus
PY - 2026
DA - 2026/10/02
JO - International journal of medical sciences
DO - 10.7150/ijms.130407
UR - https://europepmc.org/article/MED/42909893
AB - Introduction Breast cancer represents the most prevalent malignancy among women globally, with a rising incidence of metastases to the central nervous system. The presence of brain metastases is associated with a poor prognosis, largely due to the limited availability of effective treatment modalities.Methods In this preliminary study, we performed an epigenome-wide DNA-methylation analysis of matched primary breast cancer and brain metastasis of the same patients applying the Illumina Infinium EPIC Bead Chip interrogating more than 850,000 CpG sites at single base resolution.Results We found that primary breast cancers and corresponding metastases are very similar on the global DNA methylation level. Detailed analysis showed aberrant methylation patterns that reflect the process of brain metastasis. We identified 107 nominally significant methylated CpG sites (DMCGs) within promoter and gene regions (Δβ ≥ 0.1, p-value < 0.05), when comparing primary breast tumors to their brain metastatic counterparts. However, due to the limited sample size, no individual CpG site retained statistically significant after correction for multiple testing.Conclusion Our study highlights specific aberrant DNA methylation patterns that are associated with brain metastasis in breast cancer. Characterizing these epigenetic alterations provides a promising avenue for identifying novel therapeutic targets and clinically relevant biomarkers.
SN - 1449-1907
ER -