Figure 1. An inactivating mutation in FBXW7 is associated with resistance to PD-1 blockade.

(a) CT scan from a patient with metastatic melanoma with heterogenous response to the PD-1 inhibitor pembrolizumab. The patient presented with diffuse metastatic disease, which responded to treatment with the exception of a right adrenal mass. The patient’s cervical lymph node tumor was biopsied prior to treatment and right adrenal gland was biopsied upon the development of adrenal resistance. (b) Phylogic analysis of the somatic mutations identified by whole exome sequencing of the pre-treatment and resistant (right adrenal) biopsies. (c) Intersection of clonal, deleterious somatic changes identified by SIFT or PolyPhen analysis with clonal somatic mutations listed in the COSMIC database. (d) Frequency of FBXW7 mutations in cancer. R505 and R465 are known oncogenic, loss-of-function mutations in FBXW7. Green: missense mutations; black: nonsense mutations. cBioPortal, 1483 samples. Additional data in Supplementary Figure 1, Supplementary Table 1 and Supplementary Table 2.