<scp>CD</scp>99‐positive undifferentiated round cell sarcoma diagnosed on fine needle aspiration cytology, later found to harbour a <i><scp>CIC</scp>‐<scp>DUX</scp>4</i> translocation: a recently described entity

Kajtár, Béla; Tornóczky, Tamás; Kálmán, Endre; Kuzsner, József; Hogendoorn, Pancras C.W.; Szuhai, Károly

doi:10.1111/cyt.12079

Cited by 22 publications

(18 citation statements)

References 10 publications

(30 reference statements)

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“…In seven other cases with CIC-DUX4 , the DUX4 gene involved in the fusion apparently stems from the locus on 10q26 [13], [16]. The current data suggest that the CIC-DUX4 fusion defines a subgroup of primitive round cell sarcomas, different from Ewing sarcoma, with distinctive histopathology and rapid disease progression [1]–[5], [10]–[15].…”

Section: Introductionmentioning

confidence: 65%

“…The encoded protein is located in the nucleus, induces cell death, and has been reported to function as a transcriptional activator of paired-like homeodomain transcription factor 1 (PITX1) [8], [9]. So far, there are roughly 20 reported cases of sarcoma with the t(4;19)(q35;q13) and/or CIC-DUX4 fusion [1]–[5], [10]–[15]. In seven other cases with CIC-DUX4 , the DUX4 gene involved in the fusion apparently stems from the locus on 10q26 [13], [16].…”

Section: Introductionmentioning

confidence: 99%

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The “Grep” Command But Not FusionMap, FusionFinder or ChimeraScan Captures the CIC-DUX4 Fusion Gene from Whole Transcriptome Sequencing Data on a Small Round Cell Tumor with t(4;19)(q35;q13)

et al. 2014

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Whole transcriptome sequencing was used to study a small round cell tumor in which a t(4;19)(q35;q13) was part of the complex karyotype but where the initial reverse transcriptase PCR (RT-PCR) examination did not detect a CIC-DUX4 fusion transcript previously described as the crucial gene-level outcome of this specific translocation. The RNA sequencing data were analysed using the FusionMap, FusionFinder, and ChimeraScan programs which are specifically designed to identify fusion genes. FusionMap, FusionFinder, and ChimeraScan identified 1017, 102, and 101 fusion transcripts, respectively, but CIC-DUX4 was not among them. Since the RNA sequencing data are in the fastq text-based format, we searched the files using the “grep” command-line utility. The “grep” command searches the text for specific expressions and displays, by default, the lines where matches occur. The “specific expression” was a sequence of 20 nucleotides from the coding part of the last exon 20 of CIC (Reference Sequence: NM_015125.3) chosen since all the so far reported CIC breakpoints have occurred here. Fifteen chimeric CIC-DUX4 cDNA sequences were captured and the fusion between the CIC and DUX4 genes was mapped precisely. New primer combinations were constructed based on these findings and were used together with a polymerase suitable for amplification of GC-rich DNA templates to amplify CIC-DUX4 cDNA fragments which had the same fusion point found with “grep”. In conclusion, FusionMap, FusionFinder, and ChimeraScan generated a plethora of fusion transcripts but did not detect the biologically important CIC-DUX4 chimeric transcript; they are generally useful but evidently suffer from imperfect both sensitivity and specificity. The “grep” command is an excellent tool to capture chimeric transcripts from RNA sequencing data when the pathological and/or cytogenetic information strongly indicates the presence of a specific fusion gene.

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Section: Introductionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

The “Grep” Command But Not FusionMap, FusionFinder or ChimeraScan Captures the CIC-DUX4 Fusion Gene from Whole Transcriptome Sequencing Data on a Small Round Cell Tumor with t(4;19)(q35;q13)

et al. 2014

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“…The transcriptional activity of CIC is enhanced as a result of the fusion, with subsequent deregulation of downstream targets. Specifically, the CIC–DUX4 fusion oncoprotein up‐regulates the PEA3 subfamily of ETS , including ETV1 , ETV4 , and ETV5 l , thereby sharing its molecular pathogenesis, in part, with ES . The transcriptional profile of CIC–DUX4 fusion‐positive sarcomas does, however, appear to be distinct from that of ES, in parallel with a somewhat distinctive morphology and different clinical behaviour .…”

Section: Introductionmentioning

confidence: 99%

“…1,2,5 DUX4 encodes a double homeobox transcription factor, two genomic copies of which are located within polymorphic macrosatellite repeats on 4q35 and 10q26. 2,5 Its normal function is poorly understood, 5,6 and its expression is normally suppressed in differentiated cells. 1,5,6 DUX4 has been implicated in the pathogenesis of fascioscapulohumeral muscular dystrophy.…”

Section: Introductionmentioning

confidence: 99%

CIC–DUX4 fusion‐positive round‐cell sarcomas of soft tissue and bone: a single‐institution morphological and molecular analysis of seven cases

et al. 2016

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“…These sarcomas, originally characterized in the pediatric population, [2][3][4][5] have been found to occur over a wide age range, though they arise predominantly in young adults. [6][7][8][9][10] We recently reported four undifferentiated round cell sarcomas harboring CIC-DUX4 fusions, 11 which, together with reported CIC-DUX4L 6 cases, we term 'CIC-DUX sarcomas'. These tumors demonstrated clinical behavior at least as aggressive as Ewing sarcomas, with all four patients expiring from disease within 18 months.…”

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confidence: 99%

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression

et al. 2015

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Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (cMyc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas.

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CD99‐positive undifferentiated round cell sarcoma diagnosed on fine needle aspiration cytology, later found to harbour a CIC‐DUX4 translocation: a recently described entity

Cited by 22 publications

References 10 publications

The “Grep” Command But Not FusionMap, FusionFinder or ChimeraScan Captures the CIC-DUX4 Fusion Gene from Whole Transcriptome Sequencing Data on a Small Round Cell Tumor with t(4;19)(q35;q13)

The “Grep” Command But Not FusionMap, FusionFinder or ChimeraScan Captures the CIC-DUX4 Fusion Gene from Whole Transcriptome Sequencing Data on a Small Round Cell Tumor with t(4;19)(q35;q13)

CIC–DUX4 fusion‐positive round‐cell sarcomas of soft tissue and bone: a single‐institution morphological and molecular analysis of seven cases

CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression

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