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Metastasis\u2010potential and treatment\u2010resistance is thought to rely on increased plasticity of the cancer cells\u2014a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases. As cellular plasticity is largely driven by non\u2010genetic events, complementary studies in cancer epigenomics are now being conducted to identify\n                    <jats:italic>chromatin variants<\/jats:italic>\n                    . These variants, defined as genomic loci in cancer cells that show changes in chromatin state due to the loss or gain of epigenomic marks, inclusive of histone post\u2010translational modifications, DNA methylation and histone variants, are considered the fundamental units of epigenomic heterogeneity. In prostate cancer chromatin variants hold the promise of guiding the new era of precision oncology. In this review, we explore the role of epigenomic heterogeneity in prostate cancer, focusing on how chromatin variants contribute to tumor evolution and therapy resistance. We therefore discuss their impact on cellular plasticity and stochastic events, highlighting the value of single\u2010cell sequencing and liquid biopsy epigenomic assays to uncover new therapeutic targets and biomarkers. Ultimately, this review aims to support a new era of precision oncology, utilizing insights from epigenomics to improve prostate cancer patient outcomes.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35327","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T10:20:21Z","timestamp":1737627621000},"page":"314-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenomics\u2010guided precision oncology: Chromatin variants in prostate tumor evolution"],"prefix":"10.1002","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1724-7061","authenticated-orcid":false,"given":"Kira","family":"Furlano","sequence":"first","affiliation":[{"name":"Department of Urology Charit\u00e9\u2010 Universit\u00e4tsmedizin Berlin  Berlin 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