Systems epigenetic approach towards non-invasive breast cancer detection.

Herzog, Chiara M. S.; Theeuwes, Bente; Jones, Allison; Evans, Iona; Bjørge, Line; Zikan, Michal; Cibula, David; Harbeck, Nadia; Colombo, Nicoletta; Pashayan, Nora; Widschwendter, Martin

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.The suitability of non-invasive surrogate samples for detecting breast cancer remains to be systematically explored. Here, the authors compare non-invasive, non-tumour DNA methylation profiles from cervical, buccal, and blood samples and develop classifiers for breast cancer detection for each sample type.

Nature Communications, 2025, Vol 16, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-024-53696-2