We and others have demonstrated that patients with cancer with a high tumor variation burden have derived encouraging benefits from immune checkpoint inhibitor (ICI) therapy.1,2 The oncogene MUC16 (OMIM 606154) encodes cancer antigen 125, which has shown robust prognostic ability as well as critical involvement in the regulation of tumor variation burden and immune cellular dysfunction and resistance.3,4 However, there is no current clinical evidence of the association of MUC16 variation with ICI therapy benefit. Here, MUC16 is linked to cancer.