A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
Nat Genet, 2012/3/04;44(4):461-6.
Pierron G[1], Tirode F, Lucchesi C, Reynaud S, Ballet S, Cohen-Gogo S, Perrin V, Coindre JM, Delattre O
Affiliations
PMID: 22387997DOI: 10.1038/ng.1107
Impact factor: 41.307
Abstract
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; Bone Neoplasms; Cell Line; Child; Chromosomes, Human, X; Cyclin B; Female; Gene Fusion; Humans; Male; Mice; Molecular Sequence Data; NIH 3T3 Cells; Oncogene Proteins, Fusion; Osteosarcoma; Proto-Oncogene Proteins; RNA-Binding Protein EWS; Repressor Proteins; Sarcoma; Sarcoma, Ewing; Sequence Analysis, DNA; Translocation, Genetic; Young Adult
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