Molecular landscape of the discovery cohort. A, Comparison of the genetic landscape of RNF43-mut, RSPOfp, and RNF43/RSPOfp-WT tumors. Shown are mutations that are significantly different between RSPOfp and RNF43-mut tumors (all q < 0.05; ns: P < 0.05, but q < 0.05 was not reached). B, Copy-number alterations in RNF43-mut, RSPOfp, and RNF43/RSPO-WT tumors. *, q < 0.05; **, q < 0.01; and ***, q < 0.001. C, MSI, TMB, and PDL-1 status in RNF43-mut, RSPOfp and RNF43/RSPOfp-WT tumors. None of the RSPOfp patients showed a TMB >10 mt/Mb or an MSI-H/dMMR status.*, q < 0.05; **, q < 0.01; and ***, q < 0.001.