Structure and Consequences of IGH Switch Breakpoints in Burkitt Lymphoma

The t(8;14) MYC/IGH breakpoint is the hallmark translocation of human Burkitt lymphoma (BL). The translocation breakpoint most often involves the immunoglobulin heavy-chain switch regions and is thought to be brought about by an aberrant class switch recombination (CSR) event. During CSR in normal germinal center B cells, DNA double-stranded breaks are introduced in Smu and one of the downstream switch regions (Sgamma, Salpha, or Sepsilon) that are juxtaposed and ligated to form the switch junction, with deletion of the intervening DNA. In contrast, aberrant switch recombination in BL exclusively involves only one switch region, resulting in a perfect reciprocal translocation. A functional consequence of this type of translocation is that IgM expression from the chromosome affected by the translocation is not necessarily disrupted.