期刊
NATURE GENETICS
卷 44, 期 4, 页码 461-U151出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.1107
关键词
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资金
- Ligue Nationale Contre le Cancer
- Region Ile de France
- Institut National du Cancer (INCa) [2008-044, 0627, ZP09-027-EPI]
- European Union (European Embryonal Tumors pipeline)
- Courir pour Mathieu
- Dans les Pas du Geant
- Olivier Chape
- Les Bagouzamanon
- Les Amis de Claire
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.
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