The Genomic Landscape of Merkel Cell Carcinoma and Clinicogenomic Biomarkers of Response to Immune Checkpoint Inhibitor Therapy

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, which has demonstrated sensitivity to immune checkpoint inhibitor therapy. Here, we perform the largest genomics study in MCC to date to characterize the molecular landscape and evaluate for clinical and molecular correlates to immune checkpoint inhibitor response. EXPERIMENTAL DESIGN: Comprehensive molecular profiling was performed on 317 tumors from patients with MCC, including the evaluation of oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel cell polyomavirus (MCPyV). For a subset of 57 patients, a retrospective analysis was conducted to evaluate for clinical and molecular correlates to immune checkpoint inhibitor response and disease survival. RESULTS: = 0.00598, for PD-1 positive and negative, respectively). CONCLUSIONS: We provide a comprehensive genomic landscape of MCC and demonstrate clinicogenomic associates of immunotherapy response.