The bcor ccnb3 positive sarcoma is a recently identified sarcoma morphologically and clinically similar to ewing sarcoma in adolescents and young adults. Bcor immunoreactivity has recently been reported in one out of six cicpositive sarcomas,11 and also in poorly differentiated synovial sarcoma with ss18l1. Structure of the polycomb group protein pcgf1 in complex with. As seen with the bcor ccnb3 9, the entire coding sequence of bcor is also represented in the bcor maml3 fusion transcript. Bcor ccnb3 sarcoma bcs is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the ewing sarcoma es family of tumors. Ccnb3 fusion testing for all patients with ccsk who lack bcor. Bcor ccnb3 fusion sarcoma is cyclin b3positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma. Mar 03, 2012 finally, we show that ccnb3 immunohistochemistry is a powerful diagnostic marker for this group of sarcoma and that overexpression of bcor ccnb3 or of a truncated ccnb3 activates sphase in nih3t3 cells. A new subtype of bone sarcoma defined by bcor ccnb3 gene.
Oct 31, 20 bcor interacts with bcl6, and constitutional inactivating mutations of the gene have been described in the oculofacicocardiodental syndrome. Data from atlas, mitelman, cosmic fusion, fusion cancer, tcga fusion databases with official hugo symbols see references in chromosomal bands bcor xp11. Expression of cyclin d1 in clear cell sarcoma of kidney. Gene fusions involving bcor, with either ccnb3 or zc3h7b partner genes. Rnaseq results were confirmed by rtpcr and through cloning of the tumorspecific genomic translocation breakpoints. Clear cell sarcomas of the kidney are characterised by bcor gene abnormalities, including exon 15 internal tandem duplications and bcor ccnb3 gene fusion. A new subtype of bone sarcoma defined by bcor ccnb3 gene fusion. Clear cell sarcomas of the kidney are characterised by.
Whole genome sequencing analysis detected bcor exon 15internal. Bcor gene abnormalities, includin wiley online library. Novel zc3h7bbcor, meaf6phf1 and epc1phf1 fusions in. Distinct from exon 15 internal tandem duplication, in. About installation part, most of them including soapfuse, were mixed bag of different tools and hence installation was a pain. Tumors harboring a bcor ccnb3 fusion 11753 occured exclusively in males, with a mean age at diagnosis of 12. Congenital undifferentiated sarcoma associated to bcorccnb3. A third doublenegative dn category comprises ccsks with neither bcor itds nor ywhaenutm2 fusion. We analyzed copynumber alterations and fusion status in. Bcor immunoreactivity has recently been reported in one out of. Central nervous system highgrade neuroepithelial tumor with bcor alteration is a recently described entity with characteristic internal tandem duplications within exon 15 of the bcor gene hereafter. Bcorccnb3 fusions are frequent in undifferentiated sarcomas.
Bcor and ccnb3 sequences are indicated in orange and black, respectively. Development and evaluation of a pansarcoma fusion gene. However, if a fusion gene was detected in such samples with gene expression, these cases were still considered to be fusion positive. The study cohort comprised 212 cases, 96 of which showed fusion gene expression.
This targeted rna sequencing panel is a costeffective solution to detect gene fusions in multiple cancer types, regardless of origin. Unexpectedly, there is immunohistochemical positivity for bcor in this case, although no bcorccnb3 gene fusion was identified by the same technique. The normalized count values were exported to excel 2010 software microsoft, redmond. Novel bcormaml3 and zc3h7bbcor gene fusions in undifferentiated small.
Original article novel exon exon breakpoint in cicdux4. Ccnb3 exon 5 fusion gene detected by archer and one single cic. Ewing sarcoma es is a solid tumor of bone and soft tissue that primarily affects adolescents and young adults. Unexpectedly, there is immunohistochemical positivity for bcor in this case, although no bcor ccnb3 gene fusion was identified by the same technique used to identify the cicdux4 gene fusion. Wong mk, ng ccy, kuick ch, aw sj, rajasegaran v, lim jq, et al. A new subtype of bone sarcoma defined by bcorccnb3 gene fusion gaelle pierron 1,4, franck tirode 2, carlo lucchesi, stephanie reynaud, stelly ballet, sarah cohengogo. Novel exonexon breakpoint in cicdux4 fusion sarcoma. The identification of a recurrent driver mutation bcorccnb3 and a. Pierron et al identified bcor ccnb3 fusion in a subset of ewsr1negative srbct with ewing sarcoma eslike morphology. The aim of this study was to characterise 11 histologically diagnosed ccsks immunohistochemically with ccnd1, bcor and ccnb3 stains and genetically. Trusight rna fusion panel fusion detection in cancer. A new group of sarcomas is characterized by a recurrent bcor ccnb3 fusion resulting from an xchromosome paracentric inversion.
Visualisation of fusion events for the tumour located in the skin case 4 is presented in. An additional case with bcor overexpression but negative ccnb3 abnormality showed a novel kmt2d bcor fusion by targeted rnaseq. A corepressor is a protein that cannot attach bind to dna by itself, but interacts with other dnabinding proteins to suppress the activity of certain genes. A new subtype of bone sarcoma defined by bcorccnb3 gene fusion. The bcorccnb3 fusion gene, resulting from a chromosome x. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproducible diagnosis and substrates for therapy. Recently, bcorccnb3 fusions and fusions of cic with either dux4 or its paralog dux4l10 have been found in ewinglike and undifferentiated round cell sarcomas.
Recurrent ep300bcor fusions in pediatric gliomas with. Using whole transcriptome paired end rna sequencing. All patients with bcor ccnb3 gene fusion were males with a mean age at diagnosis of 12. Jun 16, 2017 the mechanism by which bcor expression is upregulated in tumors harboring bcor genetic aberrations and ywhaenutm2 gene fusions is unclear.
The same fusions have also been identified in undifferentiated sarcomas with spindled and epithelioid cells 15, 16. Nuclear dux4 expression is a promising immuno histochemical marker. In this case, the bcl6 corepressor partners with the dnabinding protein produced from the bcl6. Bcor ccnb3 associated tumors share significant clinical and pathologic similarities with ewing sarcoma, but are biologically distinct by gene expression profiling and pangenomic snp array analyses. Bcor is a robust diagnostic immunohistochemical marker of. Diagnostic yield of nanostring ncounter fusionplex profiling.
Reads were independently aligned with star alignment software against the. It is composed of larger cells than ewing sarcoma and often has prominent necrosis. Bcor and bcorl1 mutations in myelodysplastic syndromes and. In the other cases, the same fusion was verified by sanger sequencing. The bcorccnb3positive tumors occurred preferentially in children and in. In the first strategy, we applied the chimerascan fusion gene detection software by iyer et al. The bcor ccnb3 fusion gene, resulting from a chromosome x paracentric inversion, was recently described in translocationnegative ewinglike sarcomas arising in bone and soft tissue. The bcorccnb3 fusion gene, resulting from a chromosome x paracentric inversion, was recently described in translocationnegative ewinglike sarcomas arising in bone and soft tissue. Bcor ccnb3 fusions are frequent in undifferentiated sarcomas. Original article bcorccnb3 fusion and bcor internal tandem. Olivier delattre and colleagues report the discovery of a new subset of sarcoma defined by fusion of the bcor and ccnb3 genes. The bcor gene provides instructions for making a protein known as the bcl6 corepressor.
By gene expression profiling, they show that bcorccnb3positive. Undifferentiated round cell sarcomas with cicdux4 gene. In contrast to es, bcs shows consistent bcor overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring bcor genetic. The panel accommodates as little as 10 ng of total rna input or 20 ng from ffpe samples. The trusight rna pancancer panel enables the quantitative measurement of gene expression as well as the detection of gene fusions with both known and novel gene fusion partners. A new subtype of bone sarcoma defined by bcorccnb3 gene fusion, nature genetics, vol. Rnasequencing data identified one bcorccnb3 gene fusionpositive sarcoma. Bcorccnb3 undifferentiated sarcomadoes immunohistochemistry. A gene fusion involving a g nucleotide insertion in the breakpoint between exon 20 of the cic gene and exon 1 of the dux4 gene was observed in five of the cases tested in graz. We then screened a total of 75 sbrcts lacking ewsr1, fus, syt, cic, and bcor ccnb3. In total, 24 bcorccnb3positive tumors were identified among a series. A comprehensive analysis of the genomics of undifferentiated sarcomas uds is lacking. Applying pairedend rna sequencing to an sbrct index case of a 44yearold man, we identified a novel bcor maml3 chimeric fusion, which was validated by reverse transcription polymerase chain reaction and fluorescence in situ hybridization techniques.
In this group of either spindled or round cell tumors, vesicular nuclei with finely dispersed chromatin, inconspicuous nucleoli and an arciform vascular pattern were pathognomonic. Undifferentiated sarcomas in children harbor clinically. The bcor ccnb3 fusion transcript originates from a paracentric inversion on the x chromosome with an inframe fusion between the last codon of bcor and the exon 5 of ccnb3 gene. Argani p, kao yc, zhang l, bacchi c, matoso a, alaggio r, et al. Trusight rna pancancer panel study cancer gene fusions and. Bx51 fluorescent microscope tokyo, japan, controlled by imstar software paris. Thus the intrachromosomal x fusion described here represents a new subtype of bone sarcoma caused by a novel gene fusion mechanism. Puls f, niblett a, marland g, gaston cl, douis h, mangham dc, sumathi vp, kindblom lgpuls f, et al. Bcorccnb3 fusions are frequent in undifferentiated sarcomas of. Full text biomarkers in the ewing sarcoma family of. The mechanism by which bcor expression is upregulated in tumors harboring bcor genetic aberrations and ywhaenutm2 gene fusions is unclear. In total, 24 bcor ccnb3 positive tumors were identified among a series of 594 sarcoma cases. Novel bcormaml3 and zc3h7bbcor gene fusions in undifferent. Congenital undifferentiated sarcoma associated to bcor.
Bcor gene rearrangements have recently been described in a subset of small blue round cell tumors, as the 5. Ccnb3 cyclin b3 atlas of genetics and cytogenetics in. Covering 507 fusion associated genes, a single assay enables researchers to assess most known cancerrelated fusions in blood, bone marrow, and ffpe samples, with the power to identify novel fusion gene partners. A new subtype of bone sarcoma defined by bcorccnb3 gene. The patients ranged in age from 2 to 44 years old mean and median, 15, with striking male predominance m. Bcor ccnb3 sarcomas occur predominantly in children and present in the bone. Recurrent lrp1snrnp25 and kcnmb4ccnd3 fusion genes promote. By gene expression profiling, they show that bcor ccnb3 positive. Bcorccnb3 fusion and bcor internal tandem duplication in. Structure of the polycomb group protein pcgf1 in complex.
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