Whole exome sequencing (WES) and RNAseq analyses were performed in 13 biopsies from baseline lesions of advanced melanoma patients who were treated with anti-PD-1 antibody (JS001, Shanghai Junshi Biosciences, China)….several significant CNV amplifications notably only occurred in the PD cohort, such as 1q23.1, 5p15.33, 7p22.3, 11q13.3, 12q14.1, which harbor Cdk4, Ccnd1, CARD11 and mTOR genes....In summary, we discovered the genetic aberrations in the CDK4 pathways were associated with innate resistance to anti-PD-1 therapy in patients with advanced acral melanoma.