Abstract PD3-04: Chromatin remodelling is involved in resistance to CDK4/6 inhibitors in ER+ breast cancer

Abstract Background: Despite an undoubted benefit of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in estrogen receptor positive (ER+) breast cancer (BC), resistance eventually occurs. DNA-Sequencing studies identified genomic alterations that did not fully recapitulate the resistance landscape. Therefore, we explored whether changes in three-dimensional (3-D) chromatin landscape, potentially induced by single-nucleotide variants (SNVs) of non-coding regulatory regions, are involved in resistance to CDK4/6i. Methods: We generated ER+/HER2- palbociclib-resistant T47D and MCF7 BC cells (T47D-PR and MCF7-PR), by exposing parental cells to increasing doses of the drug until resistance occurred. In resistant and parental cells, we performed: 1) High-throughput Chromosome Conformation Capture (Hi-C), to investigate 3D chromatin remodelling associated with drug resistance; 2) Whole Genome Sequencing (WGS), to detect SNVs, insertions or deletions (InDels,