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While studies have classified cell lines using mutations, transcriptomics, or immunophenotypes, their DNA methylation profiles remain poorly characterised. Given the role of DNA methylation in epithelial ovarian cancer, histotype\u2010specific methylation profiling is essential to determine how accurately cell lines model primary tumours and to guide their appropriate use. The Infinium 450\u2009K and EPIC DNA methylation profiles of 60 unique ovarian cancer cell lines and 108 ovarian tumours were evaluated though a correlation and effect size analysis, focusing on genetic and epigenetic domains. DNA methylation patterns were found to be highly conserved between cell lines and tumour tissues at key transcriptional regulatory domains (CpG islands, shores, and 5\u2032 regulatory regions), with these CpG\u2010dense loci more accurately reflecting in\u00a0vivo conditions than CpG\u2010sparse regions. We identified specific cell lines with representative epigenetic signatures of high\u2010grade serous, clear cell, endometrioid, mucinous and mixed ovarian carcinoma histotypes. This study provides a framework to optimise the selection and application of ovarian cancer cell line models in DNA methylation research.<\/jats:p>","DOI":"10.1111\/jcmm.71334","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T08:05:20Z","timestamp":1787385920000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome\u2010Wide Assessment of\n                    <scp>DNA<\/scp>\n                    Methylation Fidelity Identifies Representative Ovarian Cancer Cell Line Models"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9184-6719","authenticated-orcid":false,"given":"Asia","family":"Jordan","sequence":"first","affiliation":[{"name":"School of Biology and Environmental Science, O'Brien Science Centre University College Dublin  Dublin Ireland"},{"name":"Cancer Biology and Therapeutics Laboratory UCD Conway Institute of Biomolecular and 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