Systems epigenetic approach towards non-invasive breast cancer detection
No study has systematically compared the suitability of DNA methylation (DNAme) profiles in non-invasive samples for the detection of breast cancer (BC). We assess non-tumour DNAme in 1,100 cervical, buccal, and blood samples from BC cases and controls and find that cervical samples exhibit the largest nuber of differentially methylated sites, followed by buccal samples. No sites were significant in blood after FDR adjustment. Deriving DNAme-based classifiers for BC detection in each sample type (WID-buccal-, cervical-, or blood-BC), we achieve validation AUCs of 0.75, 0.66, and 0.51, respectively. Buccal and cervical BC-associated DNAme alterations distinguish between BC cases and controls in both surrogate and breast tissue (AUC > 0.88), yet individual sites and the directionality of methylation changes are not identical between these two sample types, and buccal sample DNAme aligns with breast methylation changes more closely. Pending additional validation, these insights may have the potential to improve non-invasive personalized BC prevention.
Authors
- Nora Pashayan (ORCID: https://orcid.org/0000-0003-0843-2468)
- Line Bjørge (ORCID: https://orcid.org/0000-0002-0240-2770)
- Nadia Harbeck (ORCID: https://orcid.org/0000-0002-9744-7372)
- Chiara Herzog (ORCID: https://orcid.org/0000-0002-1572-498X)
- Martin Widschwendter (ORCID: https://orcid.org/0000-0002-7778-8380)
- Allison Jones (ORCID: https://orcid.org/0000-0003-0648-0300)
- Iona Evans (ORCID: https://orcid.org/0000-0002-0225-3154)
- Michal Zikán (ORCID: https://orcid.org/0000-0001-5266-8895)
- David Cibula (ORCID: https://orcid.org/0000-0001-6387-9356)
- Nicoletta Colombo (ORCID: https://orcid.org/0000-0003-2225-715X)
- Bente Theeuwes
Institutions
- Karolinska University Hospital (SE)
- Universität Innsbruck (AT)
- Charles University (CZ)
- University of Cambridge (GB)
- Haukeland University Hospital (NO)
- Fakultní nemocnice Bulovka (CZ)
- Karolinska Institutet (SE)
- London Women's Clinic (GB)
- Institute for Reproductive Health (US)
- General University Hospital in Prague (CZ)
- University of Bergen (NO)
- University College London (GB)
- European Institute of Oncology (IT)
- University of Milano-Bicocca (IT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-02
- DOI
- https://doi.org/10.1038/s41467-024-53696-2
- Citations
- 8
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 6.45