A high-resolution landscape of mutations in the BCL6 super-enhancer in normal human B cells.

ABSTRACT: The super-enhancers (SEs) of lineage-specific genes in B cells are off-target sites of somatic hypermutation. However, the inability to detect sufficient numbers of mutations in normal human B cells has precluded the generation of a high-resolution mutational landscape of SEs. Here we captured and sequenced 12 B cell SEs at single-nucleotide resolution from 10 healthy individuals across diverse ethnicities. We detected a total of approximately 9,000 subclonal mutations (allele frequencies <0.1%); of these, approximately 8,000 are present in the BCL6 SE alone. Within the BCL6 SE, we identified 3 regions of clustered mutations in which the mutation frequency is ∼7 × 10^-4 Mutational spectra show a predominance of C > T/G > A and A > G/T > C substitutions, consistent w

SUBMITTER: Shen JC 

PROVIDER: S-EPMC6900602 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature