Metastatic disease causes over 90% of cancer deaths, but targeted therapies are lacking due to limited understanding of its molecular mechanisms. Both genetic (SNVs and chromosome instability) and non-genetic (transcriptional reprogramming) factors contribute to metastasis, with unknown links between chromosome instability, transcriptional reprogramming, and metastasis. This project aims to investigate whether chromosome rearrangements and SNVs at GRHL2 enhancers disrupt genome architecture, weakening epithelial transcriptional programs and promoting metastatic phenotypes. Using advanced bioinformatic tools, the candidate will reconstruct GRHL2-enhancer interactions, identify relevant genes, and assess clinical significance in large patient cohorts, potentially impacting cancer research and personalized oncology.