We used duplex sequencing to detect low-frequency mutations in the BCL6 super-enhancer locus in normal human B cells. The landscape of preexisting mutations is remarkably conserved across different ethnicities and reveals clustered mutational hotspots that correlate with reported sites of clonal mutations and translocation breakpoints in human B cell lymphomas. This high-resolution genomic landscape revealed by duplex sequencing offers accurate and thorough profiling of low-frequency preexisting mutations in normal individuals along with the potential for early detection of neoplastic alterations.
