Unusual primary cerebral localization of a CIC–DUX4 translocation tumor of the Ewing sarcoma family

Bielle, Franck; Zanello, Marc; Guillemot, Delphine; Gil-Delgado, M.; Bertrand, Anne; Boch, Anne‐Laure; Fréneaux, Paul; Mokhtari, Karima

doi:10.1007/s00401-014-1312-0

Cited by 30 publications

(25 citation statements)

References 8 publications

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“…Thus the putative chimeric amino acid sequence consists only of a prematurely truncated CIC protein without a subsequent DUX4 protein. A similar truncation of predicted fusion protein was previously described in 10 CIC‐DUX4 sarcoma cases . Gambarotti et al described 2 CIC‐DUX4 fusion variants with immediate stop codons after the fusion junction .…”

Section: Discussionsupporting

confidence: 67%

“…The latter may be supported by the fact that the case previously reported by our group indeed had different fusion variants identified by 3′ rapid amplification of cDNA ends (RACE) . All the other 9 cases reported with this fusion variant were identified by RT‐PCR using the same primers . Two of the cases showed overlapping CIC and DUX4 sequences after the presumed CIC breakpoints, which could also be explained by the presence of multiple fusion variants …”

Section: Discussionsupporting

confidence: 59%

“…All the other 9 cases reported with this fusion variant were identified by RT‐PCR using the same primers . Two of the cases showed overlapping CIC and DUX4 sequences after the presumed CIC breakpoints, which could also be explained by the presence of multiple fusion variants …”

Section: Discussionmentioning

confidence: 94%

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ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

Kao

Sung

Chen

et al. 2017

Genes Chromosomes & Cancer

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CIC rearrangements have been reported in two-thirds of EWSR1-negative small blue round cell tumors (SBRCTs). However, a number of SBRCTs remain unclassified despite exhaustive analysis. Fourteen SBRCTs lacking driver genetic events by RNA sequencing (RNAseq) analysis were collected. Unsupervised hierarchical clustering was performed using samples from our RNAseq database, including 13 SBRCTs with non-CIC genetic abnormalities and 2 CIC-rearranged angiosarcomas among others. Remarkably, all 14 study cases showed high mRNA levels of ETV1/4/5, and by unsupervised clustering most grouped into a distinct cluster, separate from other tumors. Based on these results indicating a close relationship with CIC-rearranged tumors, we manually inspected CIC reads in RNAseq data. FISH for CIC and DUX4 abnormalities and immunohistochemical stains for ETV4 were also performed. In the control group, only 2 CIC-rearranged angiosarcomas had high ETV1/4/5 expression. Upon manual inspection of CIC traces, 7 of 14 cases showed CIC-DUX4 fusion reads, 2 cases had DUX4-CIC reads, while the remaining 5 were negative. FISH showed CIC break-apart in 7 cases, including 5 cases lacking CIC-DUX4 or DUX4-CIC fusion reads on RNAseq manual inspection. However, no CIC abnormalities were detected by FISH in 6 cases with CIC-DUX4 or DUX4-CIC reads. ETV4 immunoreactivity was positive in 7 of 11 cases. Our results highlight the underperformance of FISH and RNAseq methods in diagnosing SBRCTs with CIC gene abnormalities. The downstream ETV1/4/5 transcriptional up-regulation appears highly sensitive and specific and can be used as a reliable molecular signature and diagnostic method for CIC fusion positive SBRCTs.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionsupporting

confidence: 59%

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ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

Kao

Sung

Chen

et al. 2017

Genes Chromosomes & Cancer

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“…CDS represents a well‐described entity, with 59 cases having been reported in the literature . In the current WHO classification, CDSs are still included in the group of ‘undifferentiated round‐cell sarcomas’.…”

Section: Discussionmentioning

confidence: 99%

“…Seventy‐nine cases of CDS have been reported so far in the literature, mostly arising in deep or superficial soft tissue, or, very rarely, in viscera . Some of these cases are characterized by molecular variants of the classic CIC–DUX4 translocation, including CIC and alternative fusion partners.…”

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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A case report of CIC‐rearranged undifferentiated small round cell sarcoma in the cerebrum

Ito

Ishikawa

Kitajima

et al. 2016

Diagnostic Cytopathology

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CIC-rearranged undifferentiated small round cell sarcoma (CIC-rearranged USRCS) is a recently established type of Ewing-like small round cell sarcomas, characterized by CIC gene rearrangement, most commonly CIC-DUX4 fusion. This report presents the second case of CIC-rearranged USRCS arising primarily in the cerebrum. A 64-year-old otherwise healthy woman presented with a 1 × 1 cm sized hemorrhagic subcortical tumor in the left temporo-parietal lobe. The tumor repeatedly recurred, and the patient underwent three surgeries, chemotherapy with doxorubicin and ifosfamide, and radiotherapy, as well as gamma knife surgery. Systemic examination revealed no other extracranial masses. Imprint cytology revealed small to moderate-sized round-to-ovoid tumor cells with mild pleomorphism and variations in size and shape. The nuclei contained finely granular chromatin, and some had easily-recognizable nucleoli. The tumor exhibited a mainly cytoplasmic pattern of CD99 immunostaining, rather than a diffuse membranous pattern. The tumor also exhibited diffuse positivity for calretinin and p16, as well as partial positivity for WT1 (nuclear and cytoplasmic staining pattern) and D2-40. FISH assessment showed CIC split signals. In conclusion, CIC-rearranged USRCSs can occur primarily in the cerebrum. It would be impossible to diagnose them through cytology alone, but cytology would be useful to rule out other small round cell brain tumors including gliomas, lymphomas, carcinomas, and germinoma. Immunohistochemical analysis including tests for CD99, calretinin, and WT1 would help to suggest CIC-rearranged USRCSs and distinguish them from Ewing sarcomas. Additionally, immunohistochemistry for p16 might be useful in the diagnosis. Diagn. Cytopathol. 2016;44:828-832. © 2016 Wiley Periodicals, Inc.

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Unusual primary cerebral localization of a CIC–DUX4 translocation tumor of the Ewing sarcoma family

Cited by 30 publications

References 8 publications

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements

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

A case report of CIC‐rearranged undifferentiated small round cell sarcoma in the cerebrum

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