Details

Autor(en) / Beteiligte

• PIERRON, Gaëlle
• TIRODE, Franck
• LUCCHESI, Carlo
• REYNAUD, Stephanie
• BALLET, Stelly
• COHEN-GOGO, Sarah
• PERRIN, Virginie
• COINDRE, Jean-Michel
• DELATTRE, Olivier

Titel

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

Ist Teil von

• Nature genetics, 2012-04, Vol.44 (4), p.461-466

Ort / Verlag

New York, NY: Nature Publishing Group

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.