Association of RNF43 Genetic Alterations With BRAF and MSI in Colorectal Cancer.

Purpose: Recent studies have provided evidence for a predictive value of genetic alterations (GAs) as biomarkers for targeted therapies in microsatellite-stable (MSS) colorectal cancer (CRC). These data have the potential to prioritize treatment strategies in patients with -mutant CRC and help to identify a subgroup that is more likely to derive benefit versus those patients for whom alternative treatment approaches are needed. We were therefore interested in defining the precise frequency of and GAs and their respective overlap in a large cohort of patients with CRC.

Methods: To address this question, we performed a retrospective analysis that included 52,969 patients diagnosed with CRC from the FoundationCORE database.

Results: We observed a striking association of GAs with MSI and tumor mutational burden status and mutations. Overall, 23% of MSS patients with confirmed mutation harbor an GA-which accounts for 1.1% of all patients with CRC and for 15.7% of all CRC cases.

Conclusion: Ongoing phase III clinical trials, such as BREAKWATER, should aim to incorporate broader genetic profiling to further validate the superior sensitivity of patients with -mutant, MSS CRC to anti-EGFR-/BRAFi-based therapies.