Extended Data Fig. 5: Waterfall plots depicting different molecular subtypes.

A) Integrated waterfall plot showing best change in the total diameter of target lesions from baseline in 86 patients with mCRC^BRAF-V600E tumors treated with anti-BRAF/EGFR combinatory therapies (discovery cohort, n = 44, plus validation cohort, n = 42). As a common in real-world clinical practice for aggressive tumors like mCRC^BRAF-V600E, images from a proportion of patients (n = 12) were not available, mostly due to rapid clinical deterioration. B–D) Waterfall plots including patients with the different molecular subtypes: B) MSI-RNF43^mutated tumors are shown in gray, C) MSS-RNF43^wild-type tumors are shown in yellow, and D) MSS-RNF43^mutated tumors are shown in blue. E) The post-contrast CT scan at baseline shows multiple liver metastases (yellow arrows) in a patient with mCRC^BRAF-V600E with a MSS-RNF43^mutated tumor. F) The post-contrast CT scan after 3 months of treatment shows marked reduction in size of the liver metastases (yellow arrows); some of the lesions are no longer seen in the follow-up CT-scan (yellow circles). Abbreviations: MSI, microsatellite instability high; MSS, microsatellite stable.