A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion

Nat Genet. 2012 Mar 4;44(4):461-6. doi: 10.1038/ng.1107.


The identification of subtype-specific translocations has revolutionized the diagnostics of sarcoma and has provided new insight into oncogenesis. We used RNA-seq to investigate samples from individuals diagnosed with small round cell tumors of bone, possibly Ewing sarcoma, but which lacked the canonical EWSR1-ETS translocation. A new fusion was observed between BCOR (encoding the BCL6 co-repressor) and CCNB3 (encoding the testis-specific cyclin B3) on the X chromosome. RNA-seq results were confirmed by RT-PCR and through cloning of the tumor-specific genomic translocation breakpoints. In total, 24 BCOR-CCNB3-positive tumors were identified among a series of 594 sarcoma cases. Gene profiling experiments indicated that BCOR-CCNB3-positive cases are biologically distinct from other sarcomas, particularly Ewing sarcoma. Finally, we show that CCNB3 immunohistochemistry is a powerful diagnostic marker for this subgroup of sarcoma and that overexpression of BCOR-CCNB3 or of truncated CCNB3 activates S phase in NIH3T3 cells. Thus, the intrachromosomal X-chromosome fusion described here represents a new subtype of bone sarcoma caused by a newly identified gene fusion mechanism.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Base Sequence
  • Biomarkers, Tumor / genetics
  • Bone Neoplasms / genetics*
  • Cell Line
  • Child
  • Chromosomes, Human, X / genetics
  • Cyclin B / biosynthesis
  • Cyclin B / genetics*
  • Cyclin B / metabolism
  • Female
  • Gene Fusion*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Oncogene Proteins, Fusion / genetics*
  • Osteosarcoma / genetics*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA-Binding Protein EWS / genetics
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Sarcoma, Ewing / genetics
  • Sequence Analysis, DNA
  • Translocation, Genetic
  • Young Adult


  • BCOR protein, human
  • Biomarkers, Tumor
  • CCNB3 protein, human
  • Cyclin B
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RNA-Binding Protein EWS
  • Repressor Proteins

Associated data

  • GENBANK/JN813375
  • GEO/GSE34800