Abstract
MAPK signaling activation is an important driver event in colorectal cancer (CRC) tumorigenesis that informs therapy selection, but detection by liquid biopsy can be challenging. We analyze real-world comprehensive genomic profiling (CGP) data to explore the landscape of alterations in BRAF or RAS in CRC patients (N = 51 982) and co-occurrence with other biomarkers. A pathogenic RAS or BRAF alteration was found in 63.2% and 57.9% of colon and rectal cancer samples, respectively. In a subset of 140 patients with both tissue- and liquid-based CGP, the sensitivity of liquid for results found by tissue was 100% when ctDNA tumor fraction was at least 1%, illustrating the utility of tissue and liquid biopsy in detecting driver alterations in CRC.