The 12th International Symposium on 3D Genomics

Esophageal squamous cell carcinoma (ESCC) exhibits pronounced genomic instability, yet how three-dimensional (3D) genome remodeling contributes to transcriptional regulation remains unclear. Here, we generated high-resolution Hi-C maps from fluorescence-activated cell sorting (FACS)–purified tumor and matched normal epithelial cells from ESCC patients, together with ESCC cell lines and normal esophageal epithelial organoids. Integration with RNA-seq, single-cell RNA-seq, ATAC-seq, and public epigenomic datasets revealed widespread compartment switching and chromatin loop reprogramming in ESCC and identified recurrent tumor-specific loops, including enhanced enhancer–promoter interactions at AKR1C3. Structural variations further reshaped chromatin architecture by generating tumor-specific neo-loops. These results provide a high-resolution 3D genome atlas of ESCC and a spatial framework for understanding transcriptional dysregulation.