biostudies-literatureUnknown72Gonye ALNational Institutes of Health National Cancer InstituteUS Department of Defense Prostate Cancer Research ProgramChemotherapy resistance remains a critical barrier in cancer treatment, partly driven by polyploid cells that survive therapy and contribute to tumor recurrence. Here, we investigated epigenomic and transcriptional changes associated with cisplatin-surviving polyploid cells compared to parental cancer cells in prostate cancer (PC3) and triple-negative breast cancer (MDA-MB-231) cell lines. We observed persistent dysregulation of chromatin compaction and altered nuclear structure in polyploid cells following cisplatin treatment. Genome-wide chromatin accessibility profiling via ATAC-seq revealed significant remodeling, notably decreased promoter accessibility at proliferation-associated loci and increased accessibility of distal regulatory elements linked to inflammation and stress responseNeoplasia (New York, N.Y.)101268https://www.ebi.ac.uk/biostudies/studies/S-EPMC12857548biostudies-literaturePolyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status.PMC12857548Cherry COrzolek LButler GPienta KJAmend SRGonye ALTruskowski KLoftus LVPatatanian MfalsePolyploid cisplatin-resistant cancer cells have altered nuclear organization and epigenomic status.Chemotherapy resistance remains a critical barrier in cancer treatment, partly driven by polyploid cells that survive therapy and contribute to tumor recurrence. Here, we investigated epigenomic and transcriptional changes associated with cisplatin-surviving polyploid cells compared to parental cancer cells in prostate cancer (PC3) and triple-negative breast cancer (MDA-MB-231) cell lines. We observed persistent dysregulation of chromatin compaction and altered nuclear structure in polyploid cells following cisplatin treatment. Genome-wide chromatin accessibility profiling via ATAC-seq revealed significant remodeling, notably decreased promoter accessibility at proliferation-associated loci and increased accessibility of distal regulatory elements linked to inflammation and stress response2026-01-01T00:00:00Z2026 Feb2026-06-10T08:53:44.741Z2026-06-10T03:12:18.535ZS-EPMC128575484157044710.1016/j.neo.2025.101268