592 Epigenetic memory of radiation injury in skin fibroblasts of cancer patients

Radiotherapy (RT) is a common cancer treatment but often results in an unintended injury to overlying skin and contributes impaired wound healing. Skin fibroblasts (FBs) play critical roles repair. We investigated the long-term effects of RT on FB functions understand better pathological mechanisms adverse reactions RT. collected tissue biopsies from non-irradiated (RT-) irradiated (RT+) breast patients who received 1-12 years ago. found that ex vivo healing motility were significantly reduced RT+ compared paired RT- skin. next FBs for their genome-wide gene expression by RNA-sequencing (seq) chromatin accessibility ATAC-seq. Multi-omics analysis revealed promoter region thrombospondin-1 (THBS1) was more accessible than FBs, whereas its level not different between these two groups FBs. Interestingly, stimulation with TGF-β, key cytokine repair, led robust upregulation THBS1 higher RUNX1 binding Also, we observed expressed wounds generated Furthermore, showed silencing enhanced cell migration TGF-β-induced ACTA2 expression. Collectively, our study reveals isolated previously maintain increased chromosomal promoter, enabling swift induction via after stimulus such as TGF-β. The elevated may compromise patients’ capacity even long time radiotherapy.