Exploring the Prognostic Significance of Arm-Level Copy Number Alterations in Triple Negative Breast Cancer

Focal somatic copy number alterations have been extensively studied, yet the impact of larger arm-level SCNAs remains poorly understood. Our study investigated the association between arm-level SCNAs and overall survival in triple negative breast cancer. We identify frequent arm-level SCNAs, including 21q gain, which correlates with poor overall survival in TNBC patients. Through comprehensive analyses, we identified RIPK4 as having a significant expression change associated with survival. We show that targeting Ripk4 in a murine lung metastatic TNBC model significantly reduced tumor burden, improved overall survival, and modulated the tumor immune microenvironment. We found that RIPK4 allows tumor cells to survive at distant metastatic sites, such as the lungs, thereby facilitating the formation of additional metastatic lesions. Our findings highlight the significance of arm-level SCNAs in breast cancer progression and identify RIPK4 as a putative driver of TNBC metastasis and immunosuppression.