Conserved Regulatory DNA Methylation in Human and MYC/PI3K-Driven Murine EBV-Negative Burkitt Lymphoma

Background/Objectives: Burkitt lymphoma (BL) is an aggressive germinal center B-cell (gcBC) malignancy driven by MYC deregulation and cooperating molecular alterations. A mouse model combining constitutive MYC and PI3K activity in gcBC closely recapitulates key features of human BL, but its epigenetic similarity to the human disease has not been investigated in detail. Here, we compared genome-wide DNA methylation patterns between human sporadic EBV-negative BL and this murine model.

Methods

DNA methylation profiles of 37 human BL samples and 20 gcBC controls were compared with those of 8 murine tumors from the MYC/PI3K driven mouse model and 11 murine gcBC controls using Illumina methylation arrays. Differentially methylated CpGs were identified using linear modeling, and chromatin-state enrichment, cross-species gene overlap, protein interaction, and pathway enrichment analyses were performed.