{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BORCS8‐MEF2B represents an aberrant form of the MEF2B transcription factor that, under normal conditions, helps govern gene expression programs critical for B‐cell function and differentiation. Studies in non‐Hodgkin lymphomas have shown that MEF2B is recurrently mutated in germinal center–derived cancers such as diffuse large B‐cell lymphoma and follicular lymphoma, where it normally functions as a calcium‐regulated activator that, among other roles, directly upregulates the prototypical oncogene BCL6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " These mutations frequently enhance MEF2B’s transcriptional output by disrupting its interactions with key corepressors, such as CABIN1 and class II histone deacetylases, thereby deregulating chromatin architecture and promoting oncogenic gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, global mapping of the MEF2B regulome in B-cell lymphomas has implicated MEF2B in the control of genes involved in cell migration, epithelial–mesenchymal transition, and other pathways that drive malignant transformation, with specific mutations reducing DNA-binding affinity and altering downstream transcriptional networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Although MEF2B belongs to a broader MEF2 family with diverse roles in muscle, cardiac, and neuronal function, evidence in lymphoid contexts indicates that aberrant MEF2B activity—exemplified by fusion with BORCS8—can disrupt the balance normally maintained by corepressors and coactivators. This disruption likely facilitates sustained deregulated expression of targets such as BCL6 and other oncogenic drivers, thereby contributing to lymphomagenesis. Notably, studies in cardiac development also suggest that proper splicing and isoform expression of MEF2B is required for correct chamber specification, underscoring the importance of precise MEF2B regulation in multiple tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Altogether, the BORCS8‐MEF2B fusion (or aberration) is thought to promote malignant transformation through enhanced transcriptional activation and by disrupting normal chromatin modification networks. These findings provide a mechanistic rationale for targeting the deregulated transcriptional and epigenetic programs driven by altered MEF2B function in lymphoid malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ryan D Morin, Maria Mendez-Lago, Andrew J Mungall, et al. 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