Distinct MYC translocation architectures in lymphomas with sole MYC translocations vs double-hit lymphomas with BCL2 and MYC translocations. In Burkitt lymphomas and diffuse large B-cell lymphomas with sole MYC translocations, these translocations are mostly targeted to the nonproductively rearranged IGH locus, either into or near to a nonproductively rearranged IGHV gene as a mistake of SHM (A), or into one of the switch regions (often switch-μ) as a mistake of class switching (B). In double-hit high-grade lymphomas with MYC and IGH::BCL2 translocations, the MYC gene is in most instances either translocated to a nonimmunoglobulin gene, for example BCL6, coming under control of the strong BCL6 super enhancer (C), or to a downstream switch region (often switch-ε) on either the allele with the productive IGHV gene (as shown in D), or the allele with the IGH::BCL2 rearrangement. Importantly, in all these constellations of MYC translocations in HGBCL-DH-BCL2, expression of the BCR and of the translocated BCL2 gene is retained. The Eμ and the 2 IGH locus 3′ RR enhancers (red squares) drive the expression of the genes juxtaposed to them. Only 4 of the 9 IGH constant region genes are shown as yellow squares. Arrows indicate the transcriptional orientation of the genes. chr, chromosome.