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Review
. 2019 May;11(7):835-855.
doi: 10.2217/epi-2018-0195. Epub 2019 May 31.

BCOR involvement in cancer

Annalisa Astolfi  1 , Michele Fiore  2 , Fraia Melchionda  2 , Valentina Indio  1 , Salvatore N Bertuccio  2 , Andrea Pession  2   3
Affiliations
Review

BCOR involvement in cancer

Annalisa Astolfi et al. Epigenomics. 2019 May.

Abstract

BCOR is a gene that encodes for an epigenetic regulator involved in the specification of cell differentiation and body structure development and takes part in the noncanonical polycomb repressive complex 1. This review provides a comprehensive summary of BCOR's involvement in oncology, illustrating that various BCOR aberrations, such as the internal tandem duplications of the PCGF Ub-like fold discriminator domain and different gene fusions (mainly BCOR-CCNB3, BCOR-MAML3 and ZC3H7B-BCOR), represent driver elements of various sarcomas such as clear cell sarcoma of the kidney, primitive mesenchymal myxoid tumor of infancy, small round blue cell sarcoma, endometrial stromal sarcoma and histologically heterogeneous CNS neoplasms group with similar genomic methylation patterns known as CNS-HGNET-BCOR. Furthermore, other BCOR alterations (often loss of function mutations) recur in a large variety of mesenchymal, epithelial, neural and hematological tumors, suggesting a central role in cancer evolution.

Keywords: BCOR; CCSK; CNS-HGNET-BCOR; ESS; ITD; PRC1.1; PRC2; SRBCS; epigenetics; oncogenesis.

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Conflict of interest statement

Financial & competing interests disclosure

This work was supported by fund donation in memory of Maestro Claudio Abbado and by Associazione Margherita Onlus. The authors have no other relevant affiliation or financial involvement with an organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Funded writing assistance was utilized in the production of this article from Enago. No other writing assistance was utilized.

Figures

Figure 1.
Figure 1.. Structure and functional domains of BCOR, including BCL-6- and MLLT3-binding domains, ANK repeats and the PUFD domain.
A schematic representation of the exon structure is also shown below the protein domains.
Figure 2.
Figure 2.. Schematic representation of the polycomb repressive complex 1.1 model.
The core complex is composed of the catalytic enzyme RING1A/B that forms a dimer with PCGF1 through the RING finger domains, and that deposits an ubiquitin moiety to histone H2A at Lys119 (H2AK119ub). BCOR binds to PCGF1 by means of its PUFD domain, while RYBP is bound to the RAWUL domain of RING1A/B. Recruitment to chromatin is due to KDM2B that recognizes nonmethylated CpG islands by its CXXC-binding domain. Other members of the complex are SKP1, that associates with KDM2B, and USP7, acting as a deubiquitinating enzyme. PUFD: PCGF Ub-like fold discriminator.
Figure 3.
Figure 3.. Schematic representation of different BCOR alterations, including internal tandem duplications and chimeric fusion transcripts.
The numbers inside the boxes represent the exons, while open boxes indicate UTR regions. (A) ITD–BCOR, (B) BCOR–CCNB3, (C) BCOR–MAML3, (D) ZC3H7B–BCOR and (E) BCOR–RARA. ITD: Internal tandem duplication.
See this image and copyright information in PMC

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