BCOR Biology in Development and Cancer

BCOR is a transcriptional corepressor and a core component of Polycomb repressive complex 1.1 (PRC1.1) with diverse roles in development and disease. Germline loss-of-function BCOR mutations cause oculofaciocardiodental syndrome, whereas diverse somatic alterations drive various malignancies. In myeloid neoplasms, loss-of-function truncating mutations disrupt BCOR-mediated transcriptional repression and cooperate with concurrent oncogenic events. Meanwhile, BCOR fusions and internal tandem duplications define distinct tumor entities in sarcomas and brain tumors. Growing evidence indicates that these somatic alterations are not mechanistically equivalent and that the functional impact of BCOR alterations is highly context-dependent, varying across cell types and developmental stages. How these distinct mutations disrupt molecular programs to drive oncogenesis remains a central question in the field. This review summarizes the current knowledge of BCOR domain organization, its epigenetic and physiological functions, and the emerging mutational landscape in human malignancies.