PAX7 expression in sarcomas bearing the EWSR1-NFATC2 translocation

Charville, Gregory W.; Wang, Wei Lien; Ingram, Davis R.; Roy, Angshumoy; Thomas, Dafydd G.; Patel, Rajiv M.; Hornick, Jason L.; Rijn, Matt van de; Lazar, Alexander J.

doi:10.1038/s41379-018-0095-6

Cited by 11 publications

(3 citation statements)

References 25 publications

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“…Cartilaginous differentiation or osteoid‐like matrix can be seen 17 . Immunohistochemically, NFATC2 ‐rearranged sarcomas show patchy‐to‐diffuse CD99 staining, 15–17 occasionally show dot‐like keratin staining, and are positive for PAX7, 30 NKX2.2, 16 and AGGRECAN, 17 but lack FLI1 and ERG expression. Transcriptionally, NFATC2 ‐rearranged sarcomas differ from other round cell sarcomas, including Ewing sarcoma 17,31 .…”

Section: Discussionmentioning

confidence: 99%

Identification of EWSR1–NFATC2 fusion in simple bone cysts

et al. 2021

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Identification of EWSR1-NFATC2 fusion in simple bone cystsAims: Simple bone cysts are benign intramedullary tumours primarily involving the long bones in skeletally immature individuals. Several mechanisms have been proposed for their pathogenesis. Although the diagnosis is typically straightforward, the interpretation can be problematic, because of superimposed fracture causing them to resemble aneurysmal bone cysts and other tumours. EWSR1-NFATC2 or FUS-NFATC2 fusions, which are characteristic of a subset of aggressive round cell sarcomas, have been recently detected in simple bone cysts. The aim of this study was to examine the clinicopathological and molecular features in a series of simple bone cysts. Methods and results: Using RNA-based next-generation sequencing and/or fluorescence in-situ hybridisation, we investigated the presence of EWSR1 or FUS rearrangements in nine simple bone cysts. The patients were five females and four males, aged 3-23 years (median, 14 years); the tumours ranged from 19 mm to 160 mm (median, 46 mm) in size, and involved the femur (n = 3), humerus (n = 2), fibula (n = 2), tibia (n = 1), and iliac wing (n =1). We identified three cases with EWSR1-NFATC2 fusion (showing identical breakpoints to those in EWSR1-NFATC2 sarcomas) and one additional case with FUS rearrangement. Unlike in EWSR1-NFATC2 sarcomas, immunohistochemical expression of NKX3.1 and NKX2.2 was absent in two simple bone cysts tested. Conclusions: More than 40% of simple bone cysts harbour genetic alterations confirming that they are neoplastic, investigation of EWSR1 and/or FUS rearrangement may help to distinguish simple bone cysts from mimics, and NFATC2 rearrangement is not pathognomonic of malignancy.

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Section: Discussionmentioning

confidence: 99%

Identification of EWSR1–NFATC2 fusion in simple bone cysts

et al. 2021

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“…However, long survival periods, even without adjuvant therapy and the lack of reported deaths due to tumor, indicate that these tumors belong to the low-grade malignant category. The relation of EWSR1-NFATC2 -translocated tumors to the group of ESs and ESLTs is currently being controversially discussed in the literature [27, 45, 46]. Based on our experience and the review of the data from the published literature, these tumors merit consideration of a separate category.…”

Section: Discussionmentioning

confidence: 99%

EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review

Bode-Lesniewska

Fritz

Exner

et al. 2019

Sarcoma

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The spectrum of mesenchymal tumors associated with rearrangements of the EWSR1 gene has been growing in recent years due to progress in molecular detection techniques. Originally identified as the gene involved in the pathogenesis of Ewing sarcoma, the EWSR1 gene is now known to be rearranged in diverse clinical and histopathological entities. The NFATC2 gene is one of the many translocation partners of EWSR1 in gene fusions in a morphologically typical, albeit rare, subgroup of mesenchymal tumors. Little is known about the clinical characteristics of tumors containing NFATC2 gene rearrangements since most of the few reports published describe molecular rather than clinical aspects. In the current study, we report three patients with tumors carrying the EWSR1-NFATC2 gene translocation, including one rare primary tumor of soft tissues. Another patient with a benign-appearing bone tumor with a unique FUS-NFATC2 gene translocation is described. In various mesenchymal tumors (e.g., myxoid/round cell liposarcoma, low-grade fibromyxoid sarcoma, or angiomatoid fibrous histiocytoma), the FUS gene, as a member of the TET family, may be alternatively rearranged instead of the EWSR1 gene without any noticeable influence on the microscopical appearance or clinical outcome. This fact seems not to apply to mesenchymal tumors with the involvement of the NFATC2 gene because both in our experience and according to the extensive literature review, they have different properties on the morphological and molecular level. Both ESWSR1-NFATC2 and FUS-NFATC2 fusion-carrying tumors do not show microscopical or clinical features of Ewing sarcoma.

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“…Also, EWSR1-NFATc2 positive sarcomas show a striking predominance of affecting mainly male adults (Grunewald et al 2018). Thus, there is an ongoing debate whether URCS with EWSR1-NFATc2 fusion belong to EwS, or whether they represent a distinct entity (Baldauf et al 2018a;Charville et al 2018).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1–NFATc2 fusion from Ewing sarcoma

Koelsche

Kriegsmann

Kommoss

et al. 2019

J Cancer Res Clin Oncol

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Purpose: Recent studies revealed divergent gene expression patterns in Ewing sarcoma (EwS) with canonical EWSR1-ETS gene fusions and undifferentiated round cell sarcomas (URCS) with EWSR1 rearrangements fused to the non-ETS gene NFATc2. Thus, the question arises whether the latter tumors really belong to EwS. Methods:We collected five cases matching the group of URCS with EWSR1-NFATc2 fusion and performed DNA-methylation and copy number profiling. Results were compared to methylation data of 30 EwS with various EWSR1-ETS fusions and one EwS with FUS-ERG fusion, 16 URCS with CIC rearrangement and 10 URCS with BCOR alteration and a total of 81 EWSR1-associated soft tissue sarcomas including 7 angiomatoid fibrous histiocytomas, 7 clear cell sarcomas of the soft tissue, 28 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas and 29 myxoid liposarcomas.Results: Unsupervised clustering and t-distributed stochastic neighbor embedding analysis of DNA-methylation data revealed a homogeneous methylation cluster for URCS with EWSR1-NFATc2 fusion, which clearly segregated from EwS and the other subtypes. Copy number profiles of EWSR1-NFATc2 cases showed recurrent losses on chromosome 9q and segmental gains on 20q13 and 22q12 involving the EWSR1 and NFATc2 loci, respectively. Conclusion:In summary, URCS with EWSR1-NFATc2 fusion share a distinct DNAmethylation signature and carry characteristic copy number alterations, which emphasizes that these sarcomas should be considered separately from EwS.

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PAX7 expression in sarcomas bearing the EWSR1-NFATC2 translocation

Cited by 11 publications

References 25 publications

Identification of EWSR1–NFATC2 fusion in simple bone cysts

Identification of EWSR1–NFATC2 fusion in simple bone cysts

EWSR1-NFATC2 and FUS-NFATC2 Gene Fusion-Associated Mesenchymal Tumors: Clinicopathologic Correlation and Literature Review

DNA methylation profiling distinguishes Ewing-like sarcoma with EWSR1–NFATc2 fusion from Ewing sarcoma

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