Neurosurgery notes/Tumours/Tumour genetics/Epigenetics/BCOR

BCOR

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Epigenetics
BCOR L1:
  • BCORL1-CREBBP fusion (not in the WHO classification)
BCL-6 transcriptional corepressor (BCOR) gene
  • Located at Xp11.4
  • Comprises 16 exons encoding a ubiquitously expressed transcriptional repressor
  • The principal isoform, encoded by 14 exons, gives rise to a protein of 1,755 amino acids.
  • BCOR protein contains two main functional binding domains.
        • Structure and functional domains of BCOR, including BCL-6- and MLLT3-binding domains, ankyrin repeats and the PUFD domain. A schematic representation of the exon structure is also shown below the protein domains.
        Structure and functional domains of BCOR, including BCL-6- and MLLT3-binding domains, ankyrin repeats and the PUFD domain. A schematic representation of the exon structure is also shown below the protein domains.
    • BCL-6 binding domain
      • Allows binding to the POZ domain of BCL-6 and increases its function as a repressor of transcription
    • Polycomb-group RING finger homolog (PCGF) ubiquitin-like fold discriminator (PUFD)
      • A domain binding to some of the PCGF proteins forming repressive complexes involved in epigenetic histone modification.
      • BCOR is part of one of the six currently described non-canonical variants of the polycomb repressive complex 1, the PRC1.1
  • Function
    • Controls homeostasis of body development
      • Number of BCOR germinal loss of function mutations (>40 were previously identified) induce oculo-facio-cardio-dental syndrome (OFCD)
  • Disease
    • CNS tumor with BCOR internal tandem duplication
      • ITD of exon 15 → PUFD non-functioning → PRC1.1 not working → PRC1.1 unable to add an ubiquitin moiety to histone H2A at Lys119 (H2AK119ub1)
      • Internal tandem duplicates (ITD): a structure rearrangement whereby a segment of DNA is duplicated and inserted serially to the original segment
    • Retinoblastoma
    • Medulloblastoma