Congenital undifferentiated sarcoma associated to bcorccnb3. The bcorccnb3positive tumors occurred preferentially in children and in. Undifferentiated round cell sarcomas with cicdux4 gene. Bcor and ccnb3 sequences are indicated in orange and black, respectively.
Novel bcormaml3 and zc3h7bbcor gene fusions in undifferentiated small. Structure of the polycomb group protein pcgf1 in complex with. Trusight rna fusion panel fusion detection in cancer. This targeted rna sequencing panel is a costeffective solution to detect gene fusions in multiple cancer types, regardless of origin. Argani p, kao yc, zhang l, bacchi c, matoso a, alaggio r, et al. Jun 16, 2017 the mechanism by which bcor expression is upregulated in tumors harboring bcor genetic aberrations and ywhaenutm2 gene fusions is unclear. We analyzed copynumber alterations and fusion status in. 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.
Distinct from exon 15 internal tandem duplication, in. Expression of cyclin d1 in clear cell sarcoma of kidney. 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. Whole genome sequencing analysis detected bcor exon 15internal. Nuclear dux4 expression is a promising immuno histochemical marker. In the other cases, the same fusion was verified by sanger sequencing. A new subtype of bone sarcoma defined by bcor ccnb3 gene. Data from atlas, mitelman, cosmic fusion, fusion cancer, tcga fusion databases with official hugo symbols see references in chromosomal bands bcor xp11.
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. Novel zc3h7bbcor, meaf6phf1 and epc1phf1 fusions in. It is composed of larger cells than ewing sarcoma and often has prominent necrosis. The patients ranged in age from 2 to 44 years old mean and median, 15, with striking male predominance m. Using whole transcriptome paired end rna sequencing. To achieve robust results, fusion gene discovery was performed using two different strategies. Pierron et al identified bcor ccnb3 fusion in a subset of ewsr1negative srbct with ewing sarcoma eslike morphology. A third doublenegative dn category comprises ccsks with neither bcor itds nor ywhaenutm2 fusion. In total, 24 bcor ccnb3 positive tumors were identified among a series of 594 sarcoma cases. The mechanism by which bcor expression is upregulated in tumors harboring bcor genetic aberrations and ywhaenutm2 gene fusions is unclear. Gene fusions involving bcor, with either ccnb3 or zc3h7b partner genes.
Congenital undifferentiated sarcoma associated to bcor. An additional case with bcor overexpression but negative ccnb3 abnormality showed a novel kmt2d bcor fusion by targeted rnaseq. Bcor is a robust diagnostic immunohistochemical marker of. Ccnb3 cyclin b3 atlas of genetics and cytogenetics in. However, if a fusion gene was detected in such samples with gene expression, these cases were still considered to be fusion positive. By gene expression profiling, they show that bcorccnb3positive. Bcor ccnb3 fusions are frequent in undifferentiated sarcomas. Development and evaluation of a pansarcoma fusion gene. Jan 21, 2020 these discordant cases included one single bcor. In total, 24 bcorccnb3positive tumors were identified among a series.
Undifferentiated sarcomas in children harbor clinically relevant. A new group of sarcomas is characterized by a recurrent bcor ccnb3 fusion resulting from an xchromosome paracentric inversion. Bcorccnb3 fusions are frequent in undifferentiated sarcomas. Original article novel exon exon breakpoint in cicdux4. The normalized count values were exported to excel 2010 software microsoft, redmond. Visualisation of fusion events for the tumour located in the skin case 4 is presented in. Bcorccnb3 fusion and bcor internal tandem duplication in.
Novel exonexon breakpoint in cicdux4 fusion sarcoma. Full text biomarkers in the ewing sarcoma family of. Structure of the polycomb group protein pcgf1 in complex. Wong mk, ng ccy, kuick ch, aw sj, rajasegaran v, lim jq, et al. The bcorccnb3 fusion gene, resulting from a chromosome x. 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. The bcor gene provides instructions for making a protein known as the bcl6 corepressor. Ccnb3 exon 5 fusion gene detected by archer and one single cic. A new subtype of bone sarcoma defined by bcorccnb3 gene fusion, nature genetics, vol. Olivier delattre and colleagues report the discovery of a new subset of sarcoma defined by fusion of the bcor and ccnb3 genes. Bcor ccnb3 fusion sarcoma is cyclin b3positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma. Bcor gene rearrangements have recently been described in a subset of small blue round cell tumors, as the 5. The bcorccnb3 fusion gene, resulting from a chromosome x paracentric inversion, was recently described in translocationnegative ewinglike sarcomas arising in bone and soft tissue. 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 lrp1snrnp25 and kcnmb4ccnd3 fusion genes promote. 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. The panel accommodates as little as 10 ng of total rna input or 20 ng from ffpe samples. Oct 31, 20 bcor interacts with bcl6, and constitutional inactivating mutations of the gene have been described in the oculofacicocardiodental syndrome. We then screened a total of 75 sbrcts lacking ewsr1, fus, syt, cic, and bcor ccnb3. Reads were independently aligned with star alignment software against the. A comprehensive analysis of the genomics of undifferentiated sarcomas uds is lacking. 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. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproducible diagnosis and substrates for therapy. Indeed, fusion gene expression with sr 5 was detected in three cases, including one synovial sarcoma, one myoepithelioma of soft tissue, and one dermatofibrosarcoma protuberans. A new subtype of bone sarcoma defined by bcor ccnb3 gene fusion.
A new fusion was observed between bcor and ccnb3 300456 on the x chromosome. 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. A new subtype of bone sarcoma defined by bcorccnb3 gene fusion. Undifferentiated sarcomas in children harbor clinically. Bcor immunoreactivity has recently been reported in one out of. 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. Bcor ccnb3 sarcomas occur predominantly in children and present in the bone. Bcorccnb3 sarcoma bcs is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated. Diagnostic yield of nanostring ncounter fusionplex profiling. The study cohort comprised 212 cases, 96 of which showed fusion gene expression. Bcor is an epigenetic regulator and is genetically altered by mutation, deletion, or gene fusion in a range of cancers. All patients with bcor ccnb3 gene fusion were males with a mean age at diagnosis of 12. Novel bcormaml3 and zc3h7bbcor gene fusions in undifferent.
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 aim of this study was to characterise 11 histologically diagnosed ccsks immunohistochemically with ccnd1, bcor and ccnb3 stains and genetically. Original article bcorccnb3 fusion and bcor internal tandem. A new subtype of bone sarcoma defined by bcorccnb3 gene. Recurrent ep300bcor fusions in pediatric gliomas with. Bcor gene abnormalities, includin wiley online library. In the first strategy, we applied the chimerascan fusion gene detection software by iyer et al. By gene expression profiling, they show that bcor ccnb3 positive. Tumors harboring a bcor ccnb3 fusion 11753 occured exclusively in males, with a mean age at diagnosis of 12. As seen with the bcor ccnb3 9, the entire coding sequence of bcor is also represented in the bcor maml3 fusion transcript. Rnasequencing data identified one bcorccnb3 gene fusionpositive sarcoma. Bcor and bcorl1 mutations in myelodysplastic syndromes and. Bcorccnb3 fusions are frequent in undifferentiated sarcomas of. Trusight rna pancancer panel study cancer gene fusions and.
Rnaseq results were confirmed by rtpcr and through cloning of the tumorspecific genomic translocation breakpoints. In this case, the bcl6 corepressor partners with the dnabinding protein produced from the bcl6. The same fusions have also been identified in undifferentiated sarcomas with spindled and epithelioid cells 15, 16. 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. Bcor immunoreactivity has recently been reported in one out of six cicpositive sarcomas,11 and also in poorly differentiated synovial sarcoma with ss18l1. 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.
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. The identification of a recurrent driver mutation bcorccnb3 and a. Clear cell sarcomas of the kidney are characterised by. About installation part, most of them including soapfuse, were mixed bag of different tools and hence installation was a pain. A new subtype of bone sarcoma defined by bcorccnb3.
Bcorccnb3 undifferentiated sarcomadoes immunohistochemistry. Thus the intrachromosomal x fusion described here represents a new subtype of bone sarcoma caused by a novel gene fusion mechanism. 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. 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. Bcor ccnb3 fusions are frequent in undifferentiated. Puls f, niblett a, marland g, gaston cl, douis h, mangham dc, sumathi vp, kindblom lgpuls f, et al. Three cases of undifferentiated round cell sarcoma showed bcorccnb3. Clear cell sarcomas of the kidney are characterised by bcor gene abnormalities, including exon 15 internal tandem duplications and bcor ccnb3 gene fusion. Bx51 fluorescent microscope tokyo, japan, controlled by imstar software paris. Ccnb3 fusion testing for all patients with ccsk who lack bcor. 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.
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