Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics

BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age‐specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS‐associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population‐based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF‐mutant CRC and reported age were