A new subtype of bone sarcoma defined by BCOR-CCNB3 gene fusion.
Nat Genet
; 44(4): 461-6, 2012 Mar 04.
Article
en En
| MEDLINE
| ID: mdl-22387997
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Sarcoma
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Neoplasias Óseas
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Osteosarcoma
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Proteínas de Fusión Oncogénica
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Proteínas Proto-Oncogénicas
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Ciclina B
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Fusión Génica
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Animals
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Francia