DNA Methylation Profiling: Current and Emerging Uses in Gynecologic Pathology

DNA methylation profiling is emerging as a powerful ancillary molecular tool for tumor classification in gynecologic pathology. This article provides a practical overview of the technology and its emerging applications, with emphasis on diagnostically challenging settings including rare mesenchymal neoplasms (eg, uterine tumors resembling ovarian sex cord tumor, SMARCA4-deficient uterine sarcoma) and lineage-ambiguous tumors. Beyond classification, methylation profiling enables copy number analysis, tumor microenvironment deconvolution, epigenetic age estimation, and cell-free DNA-based detection, with growing relevance to gynecologic pathology, albeit mostly in research setting. Current barriers include limited access, incomplete classifier development for gynecologic entities, and the need for clinical validation.