Clear Cell Sarcoma of Kidney : Role of BCOR
Section Editor: Dharam M. Ramnani, MD
Virginia Urology, Richmond, VA, USA
Image Description
Role of BCOR in Clear Cell Sarcoma of Kidney (CCSK): About 85% of CCSKs show somatic, in-frame internal tandem duplications (ITD) in the X-linked BCOR gene located at Xp11.4 locus. It was originally reported as a BCL6 corepressor that enhances BCL-6-mediated transcriptional repression. The gene has 16 alternative exons coding several protein isoforms. The principal isoform, encoded by 14 exons, is a protein of 1755 amino acids.
The function of BCOR is primarily mediated by two domains: the BCL-6-binding domain that interacts with the transcriptional repressor BCL-6 and PUFD, a domain that is common to different proteins involved in histone regulation that binds the RAWUL domain of PCGF proteins (polycomb group RING finger homologs).
The site of ITDs is 3' end of exon 15 coding sequence, involving the PUFD domain. There are tandem duplications of 89 to 114 bp. All sequence alterations are in frame and result in six types of partial duplications composed of 30-38 amino acids. The mutant BCOR protein is markedly overexpressed in ITD-positive tumors. Anti-BCOR antibody has become available as a sensitive immunohistochemical marker for the diagnosis of CCSK.
Image source: Astolfi A et al. BCOR involvement in cancer. Epigenomics (2019) 11(7):835-855; used under Creative Commons - Attribution-NonCommercial-NoDerivatives 4.0 Unported License - CC BY-NC-ND 4.0
The function of BCOR is primarily mediated by two domains: the BCL-6-binding domain that interacts with the transcriptional repressor BCL-6 and PUFD, a domain that is common to different proteins involved in histone regulation that binds the RAWUL domain of PCGF proteins (polycomb group RING finger homologs).
The site of ITDs is 3' end of exon 15 coding sequence, involving the PUFD domain. There are tandem duplications of 89 to 114 bp. All sequence alterations are in frame and result in six types of partial duplications composed of 30-38 amino acids. The mutant BCOR protein is markedly overexpressed in ITD-positive tumors. Anti-BCOR antibody has become available as a sensitive immunohistochemical marker for the diagnosis of CCSK.
Image source: Astolfi A et al. BCOR involvement in cancer. Epigenomics (2019) 11(7):835-855; used under Creative Commons - Attribution-NonCommercial-NoDerivatives 4.0 Unported License - CC BY-NC-ND 4.0