EWSR1 (Ewing sarcoma breakpoint region 1)

2010-08-01 Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC

EWSR1

LOCATION

22q12.2

IMAGE

LEGEND

t(21;22)(q22;q12) R-banding - Courtesy Francine Mugneret

IMAGE

LEGEND

t(11;22)(q24;q12) FISH with a double color EWSR1 probe - Courtesy Francine Mugneret

LOCUSID

2130

ALIAS

EWS,EWS-FLI1,bK984G1.4

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

Spans 32.5 kb, in a centromere to telomere direction on plus strand; transcript of 2654 bp from 17 exons for the canonical form, with a coding sequence of 1971 nt.

Transcription

According to Ensembl, there are 25 transcripts, of which 16 different transcripts code for proteins.

Proteins

Description

656 amino acids for the canonical form identified in 1993 (Plougastel et al., 1993), 68.5 kDa. From N-term to C-term: a transactivation domain (TAD) containing multiple degenerate hexapeptide repeats (consensus SYGQQS) (glycine, glutamine, serine, tyrosine rich or SYGQ rich, where the tyrosine is mandatory): amino acids 1 to 285, with a site interacting with SF1 from aa 228 to 264 and an IQ domain, which binds calmodulin (aa 256-285), 3 arginine/glycine rich domains (RGG regions) (aa 300-340, 454-513 (arginine/glycine/proline rich), and aa 559-640), a RNA recognition motif (RRM or RNA-binding domain (RBD): aa 361-447), and a RanBP2 type Zinc finger (aa 518-549).

Uniform small round cells with fine chromatin and pale eosinophilic cytoplasm (left); transmembrane glycoprotein MIC2/CD99 (right) - Courtesy Francine Mugneret

Expression

EWSR1 is ubiquitely expressed (Alliegro and Alliegro, 1996; Andersson et al., 2008). In particular, EWSR1 is required for cell survival in the central nervous system (Azuma et al., 2007).

Localisation

Mainly in the nucleus. It has also been found in the cytoplasm, and associated with the plasma membrane. Expression of EWSR1 in the various subcellular compartments is affected by the methylation state of its RNA-binding domain (Belyanskaya et al., 2003).
EWSR1 is mainly found in the nucleus, and more rarely in the cytoplasm than its two homologs FUS and TAF15; the 3 proteins participate in nucleo-cytoplasmic shutlling; EWSR1 localized poorly in stress granules when cells were exposed to environmental stress (stress granules are cytoplasmic particles composed of translation pre-initiation complexes, mRNAs and RNA-binding proteins) (Andersson et al., 2008), in Cajal bodies, and nucloli. Localization of EWSR1 in different subcellular compartments reflects a dynamic distribution during cell cycle: predominant nuclear localization in interphase cells, perichromosomal localization in prometaphase cells, and cytoplasmic localization in metaphase cells, association with microtubules in quiescent cells (Leemann-Zakaryan et al., 2009).

Function

RNA binding protein, single strand DNA binding.
Role in transcriptional regulation for specific genes and in mRNA splicing: Transcription and pre-mRNA slicing, a post-transcriptional activity, are closely related.
EWSR1 plays a role in transcription initiation: EWSR1 is able to associate with the basal transcription factor TFIID (a multiprotein complex composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFIIs)) and the RNA polymerase II complex. EWSR1 acts as a transcriptional activator (Bertolotti et al., 1998). It associates with heterogeneous RNA-binding proteins (hnRNPs), such as RBM38 and RBM39 (RNA binding motif proteins 38 and 39, 20q13 and 20q11 respectively) (Zinszner et al., 1994).
EWSR1 associates with EP300 and CREBBP. EWSR1 functions as a co-activator of CREBBP-dependent transcription factors. EWSR1-EP300/CREBBP mediates FOS activation, as well as HNF4 genes activation (Rossow and Janknecht, 2001; Araya et al., 2003). CREBBP is a transcription co-activator which enables the interaction between various transcription factors and RNA Pol II, brings enzymes to the promoter, and remodels the chromatin favouring the open status (Gervasini, 2009).
EWSR1 also activates other transcription factors such as POU4F1 (or BRN3A, 13q13) (Gascoyne et al., 2004), POU5F1 (or OCT4, 6p21) (Lee et al., 2005).
SF1 (splicing factor 1, 11q13, also called ZFM1) represses the transactivation domain of EWSR1; SF1, a transcription activator or repressor involved with many pathways, may negatively modulate transcription of target genes coordinated by EWSR1 (Zhang et al., 1998).
EWS functions as a docking molecule by recruiting serine-arginine (SR) splicing factors such as SRSF10 (serine/arginine-rich splicing factor 10, 1p36, or TASR, which represses pre-mRNA splicing) to RNA Pol II, coupling gene transcription to RNA splicing by binding to hyperphosphorylated RNA Pol II through its N-term part domain, and SR splicing factors through its C-term domain (Yang et al., 2000).
YBX1 (Y box binding protein 1, 1p34), a multifunctional protein that shuttles between the cytoplasm (where it binds to mRNA and regulates mRNA translation) and the nucleus (where it regulates transcription of diverse target genes), interacts with the C-term domain of EWS. This interaction docks YBX1 to RNA Pol II to participate in pre-mRNA splicing (Chansky et al., 2001).
SMN1 (survival of motor neuron 1, telomeric, 5q13) plays a major role in the pre-mRNA splicing machinery (role in spliceosomal snRNP assembly in the cytoplasm and in pre-mRNA splicing in the nucleus) (Pellizzoni et al., 1998). SMN1, through its Tudor region, binds the RG1 region of EWSR1 (Young et al., 2003).
RNU1-2 (RNA, U1 small nuclear 2, 1p36, also called U1C), another splicing protein, also interacts with EWSR1 (Knoop and Baker, 2000).
EWSR1 is phosphorylated by PRKC (protein kinase C) though its IQ domain, which inhibits RNA binding of EWSR1; CALM (calmodulin) binding to EWSR1 inhibits PRKC phosphorylation (Deloulme et al., 1997).
EWSR1 interacts with POU4F2 (4q31), a gene which regulates differentiation of neuronal cells (Gascoyne et al., 2004). EWSR1 interacts with LMNA (lamin A/C, 1q22, a component of the nuclear envelope which interacts with DNA, histones and transcriptional repressors) is essential for pre-B lymphocyte development and, during meiosis, in XY pairing and in meiotic recombination, as cross-overs are reduced in ews-/- spermatocytes. Loss of EWSR1 results in premature cellular senescence (Li et al., 2007). EWSR1 is required for proper localization of aurora B during mitosis, and maintains mitotic spindle integrity (Azuma et al., 2007).
It also interacts with BARD1 (BRCA1 associated RING domain 1) (Spahn et al., 2002).
EWSR1 and CCNL1 (cyclin L1, 3q25), are interacting partners of TFIP11 (tuftelin-interacting protein 11, 22q12), a protein functionally related to the spliceosome and involved in pre-mRNA splicing) (Tannukit et al., 2008).

Homology

Member of the TET family of RNA binding proteins, with FUS (TLS) and TAF15 (TAFII68). TET is for Tls, Ewsr1, TafII68). TET proteins contain specific structural domains not found elsewhere in other RNA binding proteins, i.e. a N-term SYGQ rich (TAD: transactivation domain), a conserved RNA-binding domain (RRM: RNA recognition motif), RG rich regions, and a Cys2-Cys2 Zinc finger which can bind nucleic acids; they are also functionally related (reviews in Law et al., 2006; Tan and Manley, 2009).

Implicated in

Entity name

Various tumours (see details below)

Entity name

Ewings sarcoma/Peripheral neurectodermal tumour (ES/PNET)

Note

- With: t(11;22)(q24;q12) --> FLI1 - EWSR1 (Delattre et al., 1992; Bailly et al., 1994; Thomas et al., 1994; records in the Mitelman Database).
- With: t(2;22)(q36;q12) --> FEV - EWSR1 (Llombart-Bosch et al., 2000; Peter et al., 2001; Navarro et al., 2002; Hattinger et al., 1999; Wang et al., 2007).
- With: t(7;22)(p22;q12) --> ETV1 - EWSR1 (Jeon et al., 1995; Peter et al., 2001; Zielenska et al., 2001; Wang et al., 2007).
- With: t(17;22)(q21;q12) --> ETV4 - EWSR1 (Kaneko et al., 1996; Urano et al., 1996; Urano et al., 1998).
- With: inv(22)(q12q12) --> PATZ1 - EWSR1 (Mastrangelo et al., 2000)
- With: t(21;22)(q21;q12) --> ERG - EWSR1 (Dunn et al., 1994; Giovannini et al., 1994; Kaneko et al., 1997; Maire et al., 2008; Minoletti et al., 1998; Sorensen et al., 1994; Zoubek et al., 1994; Zucman et al., 1993b; Shing et al., 2003; Peter et al., 1996).
Note: Rare cases of ES/PNET have been described without EWSR1 involvement, but, instead:
- with: t(2;16)(q35;p11) --> FUS - FEV (Navarro et al., 2002) or,
- with: t(16;21)(p11;q22) --> FUS - ERG (Shing et al., 2003; Berg et al., 2009). To be noted that the same t(16;21)(p11;q22) has been found in rare cases of acute myeloid leukaemia.
A t(11;22)(q24;q12) has also been found in a case of cerebellar PNET (Jay et al., 1996).

Disease

Ewings sarcoma/Peripheral neurectodermal tumour spectrum is a group of sarcomas with small blue round cells with more (PNET side) or less (Ewing side) features of neuroectodermal differentiation. ES/PNET entity also includes peripheral neuroepithelioma and Askin tumour. These tumours display both mesenchymal stem cell and neural crest stem cell properties. It is mainly found in adolescents and young adults. Cytogenetics and immunochemistry are essential for the differential diagnosis with other sarcomas (review in Romeo and Dei Tos, 2010).

Prognosis

Prognosis has dramatically improved, from less than 10% of long survivors, to a 5-year disease free survival of 75% for patients with a localized disease, and 25-30% for those with a metastatic disease (Ludwig, 2008).

Cytogenetics

The t(11;22)(q24;q12) EWSR1/FLI1 is found in 85% of cases of Ewing tumours. The t(21;22)(q21;q12) with EWSR1/ERG is the second in frequency, found in about 10% of cases.

Hybrid gene

t(11;22)(q24;q12): 5 EWSR1 - 3 FLI1; breakpoints clustered over a 2-3 kb genomic region and over a 30-40 kb genomic region. Various junctions between EWSR1 exon 7 or 10 with FLI1 exon 5, 6, or 8. In the most common fusion type (type 1), EWSR1 exon 7 is fused in frame to FLI1 exon 6; in type 2, EWSR1 exon 7 is fused in frame to FLI1 exon 5. (Obata et al., 1999; de Alava et al., 1998).
t(21;22)(q21;q12): 5 EWSR1 - 3 ERG; the orientation of the ERG gene is from telomere to centromere, opposite to that demonstrated for EWSR1.
Other translocations: 5 EWSR1 - 3 FEV; 5 EWSR1 - 3 ETV1; 5 EWSR1 - 3 ETV4; 5 EWSR1 - 3 NFATC2; 5 EWSR1 - 3 PATZ1.

Fusion protein

t(11;22)(q24;q12): oncogenic protein on the der(22) chromosome generated by fusion of the N terminal domain of EWSR1 protein (transactivation domain, e.g. fusion of EWSR1 amino acids 1-265) with the DNA binding domain (ETS type, amino acids 281-361) of the human FLI1 protein, a 452 amino acids protein (e.g. fusion from amino acids 260).
t(21;22)(q21;q12): oncogenic protein on the der(22) chromosome generated by fusion of the N terminal domain of EWSR1 protein with DNA binding domain of human ERG protein.
Other translocations: Most of the EWSR1 partners in ES/PNET are ETS family members (FLI1, ERG, ETV1, ETV4, FEV) and translocation results in the juxtaposition of the transactivation domain of EWSR1 with the DNA binding domain -ETS type of the partner. PATZ1 is a transcription regulator with a AT hook (DNA-binding motif), a POZ domain (mediates dimerisation) and Zn fingers (DNA-binding). NFATC2 is a cytokine inducer; translocates into the nucleus to regulate transcription.

Oncogenesis

EWSR1-FLI1 is a dominant oncogene transformed cells by subverting normal transcriptional controls/FLI1 member of ETS family. The target gene repertoire of EWSR1-FLI1 varies according to the host cell type. EWSR1-FLI1 induces a TP53-dependent growth arrest in fibroblasts, supporting the importance of TP53 loss in the genesis of Ewings tumours (Lessnick et al., 2002). EWSR1-FLI1 activates CASP3 and promotes apoptosis in mouse embryonic fibroblasts (Sohn et al., 2010). EWSR1-FLI1 induces expression of the embryonic stem cell genes OCT4, SOX2, and NANOG in paediatric mesenchymal stem cells but not in adult mesenchymal stem cells. SOX2 is a target for EWSR1-FLI1 and miRNA145 and may be critical in Ewing sarcoma pathogenesis (Riggi et al., 2010). EWSR1-FLI1 expression in a rhabdomyosarcoma cell line induced upregulation of many genes involved in neural crest differentiation, and the cell phenotype was modified, resembling ewing tumour cells (Hu-Lieskovan et al., 2005; Riggi et al., 2008). EZH2 is a target of EWSR1-FLI1. EZH2 regulates stemness and genes involved in neuroectodermal and endothelial differentiation (Richter et al., 2009). EWSR1-FLI1 induced T-cell neoplasia in committed lymphoid cells, showing that the oncogenetic potential of EWSR1-FLI1 is not restricted to pluripotent progenitors or mesenchymal cells (Codrington et al., 2005). EWSR1-FLI1 in transgenic mouse induced limb developmental defects by disruption of the normal development of connective tissues; homozygous deletion of p53 in mice provoke sarcomas, in particular osteosarcomas, introduction of EWSR1-FLI1 changed the tumour phenotype from osteosarcomas to poorly differentiated sarcomas (Lin et al., 2008). It is believed that EW/PNET arise from mesenchymal stem cells in which terminal differentiation is blocked by EWSR1-FLI1 (Tirode et al., 2007).
Transcriptional repressors such as NKX2-2 (Smith et al., 2006) or NR0B1 are induced by EWSR1-FLI1. Furthermore, EWSR1-FLI and NR0B1 physically interact (Kinsey et al., 2009). The transcriptional complex of EWSR1-FLI1 includes RNA polymerase II, CREB1 (cAMP responsive element binding protein 1) and DHX9 (RHA, RNA helicase A) (Toretsky et al., 2006; Erkizan et al., 2009). EWSR1-Ets proteins cooperatively bind DNA with FOS-JUN (Kim et al., 2006). EWSR1-FLI1 is involved in the spliceosome (review in Erkizan et al., 2010). EWSR1-FLI1 chimeric protein, but not wild EWSR1, can oppose the change in splicing pattern induced by expression of hnRNPA1 (Knoop and Baker, 2001).
EWSR1-FLI1 (dis)regulates many pathways (Jedlicka, 2010). CD99, a transmembrane protein highly expressed in Ewing sarcoma cells, has a key role in various biological functions, including inhibition of neuronal differentiation that may occur through the RAS/RAF/MAPK pathway in Ewings tumours (Rocchi et al., 2010). PDGFC (Zwerner and May, 2001) as well as IGF1 are induced by EWSR1-FLI1, and also by EWSR1-ERG or FUS-ERG (Cironi et al., 2008). GLI1 is upregulated by EWSR1-FLI1, independently of the Hedgehog pathway (Beauchamp et al., 2009; Joo et al., 2009). Expression of DKK1 (which antagonizes Wnt signaling) is inhibited by EWSR1-FLI1 (Navarro et al., 2010), and DKK2 enhanced (Miyagawa et al., 2009). TGFbR2 is inhibited by EWSR1-FLI1 (Hahm, 1999).
Other features were summarized in Janknecht et al., 2005: EWSR1-FLI1 induces proliferation independent of exogenous growth factors (EWSR1-ETS proteins upregulate PDGFC and also CCND1), evasion of growth inhibition (downregulation of TGFbR2 may help cells escape growth surveillance), suppression of differentiation (ID2, overexpressed in Ewing tumours, is able to suppress differentiation of a variety of cells), immortality (hTERT (human telomerase reverse transcriptase)), limiting factor for telomerase activity and senescence, is upregulated by EWSR1-ETS fusion proteins), escape from apoptosis (EWSR1-FLI1 was shown to repress IGFBP-3, preventing apoptosis) (Janknecht et al., 2005).

Entity name

Desmoplastic small round cell sarcoma (DSRCT)

Note

- With: t(11;22)(p13;q12) --> WT1 - EWSR1 (Ladanyi and Gerald, 1994; Gerald et al., 1995; Benjamin et al., 1996; records in the Mitelman Database).
- With: t(21;22)(q21;q12) --> ERG - EWSR1 (Ordi et al., 1998).

Disease

Desmoplastic small round cell sarcoma is a small blue round cells tumour, often intra-abdominal, with a male predominance, arising in children and young adults, with a very poor prognosis. Cytogenetics and immunochemistry are essential for the differential diagnosis with other sarcomas with small blue round cells.

Cytogenetics

Most of the cases are cases of t(11;22)(p13;q12).

Hybrid gene

t(11;22)(p13;q12): 5 EWSR1 - 3 WT1; breakpoints: between EWSR1 exons 7 and 8 and between WT1 exons 7 and 8.
t(21;22)(q21;q12): 5 EWSR1 - 3 ERG.

t(11;22)(q24;q12) G-banding (left) and R-banding (right) - Courtesy Francine Mugneret

Fusion protein

Transcription activator.

Oncogenesis

N terminal domain of EWSR1 fused to the Zn fingers of WT1.

Entity name

Clear cell sarcoma of soft parts/malignant melanoma of soft parts (CCSSP)

Note

- With: t(2;22)(q34;q12) --> CREB1 - EWSR1 (Antonescu et al., 2006; Wang et al., 2009).
- With: t(12;22)(q13;q12) --> ATF1 - EWSR1 (Zucman et al., 1993a; records in the Mitelman Database).

Disease

Clear cell sarcoma of tendons and aponeuroses affects young adults. It is characterized by slow progression, with recurrences and metastases, with only 40-50% long survivors.

Hybrid gene

5 EWSR1 - 3 ATF1 (t(12;22)(q13;q12) cases) or, more rarely, 5 EWSR1 - 3 CREB1 (t(2;22)(q33;q12) cases).

Fusion protein

N terminal domain of EWSR1 fused to the bZIP domain of CREB1 or ATF1.

Entity name

Angiomatoid fibrous histiocytoma (AFH)

Note

- With: t(2;22)(q34;q12) --> CREB1 - EWSR1 (Antonescu et al., 2007; Shao et al., 2009; Rossi et al., 2007).
- With: t(12;22)(q13;q12) --> ATF1 - EWSR1 (Dunham et al., 2008; Hallor et al., 2005; Hallor et al., 2007; Rossi et al., 2007; Tanas et al., 2010).
Note: Cases of t(12;16)(q13;p11) with 5 FUS - 3 ATF1 have also been described (Raddaoui et al., 2002; Waters et al., 2000).

Disease

Angiomatoid fibrous histiocytoma is a rare soft-tissue tumour of low metastatic potential (local recurrence below 15% of cases, and metastases occur in less than 2% of patients); it is mostly found in children and young adults. Surgical excision is the treatment of choice.

Hybrid gene

5 EWSR1 - 3 ATF1 (t(12;22)(q13;q12) cases), or 5 EWSR1 - 3 CREB1 (t(2;22)(q33;q12) cases).

Fusion protein

N terminal domain of EWSR1 fused to the bZIP domain of ATF1 or CREB1.

Entity name

Extraskeletal myxoid chondrosarcoma (EMCS)

Disease

Extra-skeletal myxoid chondrosarcomas represent about 5% of chondrosarcomas. There is male predominance. It affects adults mainly, in the forties or the fifties. The estimated 5-, 10-, and 15-year survival rates were 90%, 70%, and 60%, respectively (Meis-Kindblom et al., 1999).

Cytogenetics

t(9;22)(q22;q12) --> NR4A3 - EWSR1 (Labelle et al., 1995; Brody et al., 1997).
Note: Cases of t(3;9)(q12;q31) --> NR4A3 - TFG (Hisaoka et al., 2004), t(9;15)(q31;q21) --> NR4A3 - TCF12 (Sjögren et al., 2000), t(9;17)(q22;q11) --> NR4A3 - TAF15 (Sjögren et al., 1999; Attwooll et al., 1999; records in the Mitelman Database) have also been reported.

Hybrid gene

5 EWSR1 - 3 NR4A3 (NR4A3 is also known as TEC or CHN).

Entity name

Myxoid liposarcoma/round cell liposarcoma (MLS)

Disease

Myxoid liposarcoma is the most frequent type of liposarcoma, found in about half of the cases. It occurs in male and female patients equally, in their thirties to fifties. It has a relatively favorable prognosis; the variant round cell liposarcoma is much more aggressive.

Cytogenetics

A t(12;22)(q13;q12) --> DDIT3 - EWSR1 (Panagopoulos et al., 1994) is found in 5% of cases, whereas a t(12;16)(q13;p11) is found in most cases.

Hybrid gene

5 EWSR1 - 3 DDIT3 (also called CHOP). The t(12;16)(q13;p11) with 5 FUS - 3 DDIT3 is more frequent.

Fusion protein

Fuses the N-term transactivation domain of EWSR1 with the bZIP domain of DDIT3.

Entity name

Acute leukaemia

Disease

Acute lymphoblastic leukaemia (B-cell ALL), biphenotypic leukaemia

Cytogenetics

A t(12;22)(p13;q12) was found in 2 cases (Martini et al., 2002). Note: the equivalent t(12;17)(p13;q11) --> TAF15 - ZNF384 has also been found in other cases of the same series.

Hybrid gene

5 EWSR1 - 3 ZNF384.

Fusion protein

Fuses the N-term transactivation domain of EWSR1 with the leucine-serine rich-proline-nuclear localization signal-Kruppel-type C2H2 Zinc finger domains of ZNF384.

Note

EWSR1 involvement has also been described in a number of other tumours. In some instances, the diagnosis is unambiguous; in other cases, pathological diagnoses are difficult to reach, when the tumour is undifferentiated or polyphenotypic.

Entity name

Rhabdomyosarcoma (RMS)

Disease

Rhabdomyosarcomas, the most common pediatric soft tissue sarcomas, are tumours related to the skeletal muscle lineage. The 2 major subtypes are alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). Most ARMS cases are characterised by either a t(2;13)(q35;q14), resulting in a PAX3 - FOXO1 hybrid gene, or a t(1;13)(p36;q14) resulting in a PAX7 - FOXO1 hybrid gene (Reichek and Barr, 2009). However, 4 cases of RMS have been described, instead, with an EWSR1 rearrangement.

Cytogenetics

A t(4;22)(q35;q12) was found in a case of embryonal rhabdomyosarcoma (Sirvent et al., 2009), and a t(11;22)(q24;q12) in the other cases (Sorensen et al., 1993; Thorner et al., 1996).

Hybrid gene

5 EWSR1 - 3 DUX4 in the t(4;22)(q35;q12) case, and 5 EWSR1 - 3 FLI1 in the t(11;22) cases.

Entity name

Giant cell tumour of bone

Disease

Locally destructive tumour, usually seen in patients over 20 years of age, with good prognosis, despite of recurrences and pulmonary metastases (Forsyth and Hogendoorn, 2003).

Cytogenetics

In giant-cell tumour of bone, the most frequent finding is telomeric association. One study showed that a very minor clone with EWSR1/FLI1 translocation could be detected in most of the cases studied (Scotlandi et al., 2000).

Hybrid gene

5 EWSR1 - 3 FLI1.

Entity name

Myoepithelioma/myoepithelial carcinoma of soft parts

Disease

Myoepithelioma tumours of soft tissue cover a wide range of tumours of various behaviour. While most are of intermediate aggressivity, some metastase.

Cytogenetics

t(1;22)(q23;q12) in one case (Brandal et al., 2008), t(19;22)(q13;q12) in another case (Brandal et al., 2009).

Hybrid gene

5 EWSR1 - 3 PBX1, which fuses exons 8 from EWSR1 to exons 5 of PBX1 in the most benign case; 5 EWSR1- 3 ZNF444 in the malignant case; fuses EWSR1 exon 8 to the very near end of ZNF444.

Entity name

Hidradenoma of the skin

Disease

Hidradenoma or eccrine/apocrine acrospiroma, is a benign adnexal tumour developing most often in adults. 3 cases were found with a t(6;22)(p21;q12) and/or its fusion transcript equivalent (Möller et al., 2008).

Fusion protein

5 EWSR1 - 3 POU5F1.

Entity name

Mucoepidermoid carcinoma of the salivary glands

Disease

Mucoepidermoid carcinoma is the most common type of malignant salivary gland tumour, often associated with a t(11;19)(q21;p13) translocation with expression of chimeric genes 5 CRTC1 - 3 MAML2. One case of mucoepidermoid carcinoma was found with a t(6;22)(p21;q12) (Möller et al., 2008).

Fusion protein

5 EWSR1 - 3 POU5F1.

Entity name

Neuroblastoma

Disease

Neuroblastomas are peripheral neuroblastic tumours derived from cells of the sympathetic nervous system. They occur mainly in infants and young children, with a median age of 1.5 years.

Hybrid gene

Two patients, aged 3 years and 5.5 years, were described with a 5 EWSR1 - 3 FLI1 transcript in typical neuroblastomas with elevated urinary catecholamines. Prognosis had been very poor: the two patients relapsed during -or at the end of- treatment and died within 2 months (Burchill et al., 1997).

Entity name

Olfactory neuroblastoma

Disease

Olfactory neuroblastoma or esthesioneuroblastoma, is a malignant neurectodermal tumour, from the olfactory neuroepithelium that typically occurs in the superior nasal cavity. It is keratin negative, neuroendocrine marker positive, and S100 positive. It arises at any age, often in the adult, with a 5-year survival rate above 50% (the 5-year overall survival for patients treated for nonmetastatic olfactory neuroblastoma was recently found at 64% (Ozsahin et al., 2010)).

Cytogenetics

t(11;22)(q24;q12), inducing a 5 EWSR1 - 3 FLI1 hybrid gene (Sorensen et al., 1996). However, recent review rejects cases with EWSR1 involvement, as being misdiagnosed cases of ES/PNET (Thompson, 2009).

Entity name

Solid pseudopapillary tumour of the pancreas (SPTP)

Disease

Solid pseudopapillary tumour of the pancreas is a rare epithelial tumour, typically occuring in young female patients, rarely metastasizing (Yu et al., 2010).

Cytogenetics

One case showed a t(11;22)(q24;q12) (Maitra et al., 2000)

Hybrid gene

5 EWSR1 - 3 FLI1.

Entity name

"Small round cell tumours", "polyphenotypic mesenchymal malignancies", and "undifferentiated sarcomas"

Disease

An undifferentiated sarcoma derived from pelvic bone exhibited a t(6;22)(p21;q12) with 5 EWSR1 - 3 POU5F1. This resulted in the fusion of exons 1-6 of EWSR1 and exons 2-5 and a part of exon 1 of POU5F1.The patient died 6 months after diagnosis (Yamaguchi et al., 2005).
A small round cell tumour was found to have a t(2;22)(q31;q12), with 5 EWSR1 - 3 SP3 hybrid gene; fuses the exon 7 of EWSR1 to exon 6 of SP3. N-term transactivation domain of EWSR1 fused with the Zinc fingers of SP3. The patient died 20 months after diagnosis (Wang et al., 2007).
Other cases of spindle cell tumours, small round cell poorly differentiated, biphenotypic (myogenic/neural differentiation), or polyphenotypic sarcomas present with the classical t(11;22)(q24;q12) / 5 EWSR1 - 3 FLI1 or other variants, such as the t(2;22)(q36;q12) / 5 EWSR1 - 3 FEV (Wang et al., 2007), the t(11;22)(p13;q12) / 5 EWSR1 - 3 WT1 (Alaggio et al., 2007), the t(12;22)(q13;q12) / 5 EWSR1 - 3 ATF1 (Somers et al., 2005), or the t(21;22)(q21;q12) / 5 EWSR1 - 3 ERG (Tan et al., 2001).

Breakpoints

Note

Clustered over a 2.3 kb genomic region.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
17325488	2007	Spindle cell tumor with EWS-WT1 transcript and a favorable clinical course: a variant of DSCT, a variant of leiomyosarcoma, or a new entity? Report of 2 pediatric cases.	Alaggio R et al
8631501	1996	A nuclear protein regulated during the transition from active to quiescent phenotype in cultured endothelial cells.	Alliegro MC et al
18620564	2008	The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response.	Andersson MK et al
17724745	2007	EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma.	Antonescu CR et al
12459554	2003	Cooperative interaction of EWS with CREB-binding protein selectively activates hepatocyte nuclear factor 4-mediated transcription.	Araya N et al
11431376	2001	The COOH-terminal domain of FLI-1 is necessary for full tumorigenesis and transcriptional modulation by EWS/FLI-1.	Arvand A et al
10602520	1999	Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma.	Attwooll C et al
17912356	2007	Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo.	Azuma M et al
8164678	1994	DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.	Bailly RA et al
19189974	2009	GLI1 is a direct transcriptional target of EWS-FLI1 oncoprotein.	Beauchamp E et al
12915128	2003	Expression and subcellular localization of Ewing sarcoma (EWS) protein is affected by the methylation process.	Belyanskaya LL et al
8827070	1996	Fusion of the EWS1 and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors.	Benjamin LE et al
19737655	2009	Ewing sarcoma-peripheral neuroectodermal tumor of the kidney with a FUS-ERG fusion transcript.	Berg T et al
9488465	1998	EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes.	Bertolotti A et al
19760602	2009	t(19;22)(q13;q12) Translocation leading to the novel fusion gene EWSR1-ZNF444 in soft tissue myoepithelial carcinoma.	Brandal P et al
9060841	1997	Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma.	Brody RI et al
9135495	1997	EWS-FLI1 fusion transcripts identified in patients with typical neuroblastoma.	Burchill SA et al
11325824	2001	Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by YB-1 protein.	Chansky HA et al
18648544	2008	IGF1 is a common target gene of Ewing's sarcoma fusion proteins in mesenchymal progenitor cells.	Cironi L et al
15974803	2005	The Ews-ERG fusion protein can initiate neoplasia from lineage-committed haematopoietic cells.	Codrington R et al
1522903	1992	Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.	Delattre O et al
9341188	1997	The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain.	Deloulme JC et al
9242212	1997	Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors.	Desmaze C et al
18300800	2008	Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes.	Dunham C et al
8076344	1994	ERG gene is translocated in an Ewing's sarcoma cell line.	Dunn T et al
20547696	2010	Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma.	Erkizan HV et al
15021903	2004	The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1.	Gascoyne DM et al
7862627	1995	Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.	Gerald WL et al
8040301	1994	EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations.	Giovannini M et al
17106916	2006	An in vitro enzymatic assay coupled to proteomics analysis reveals a new DNA processing activity for Ewing sarcoma and TAF(II)68 proteins.	Guipaud O et al
10581042	1999	Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1 oncoprotein.	Hahm KB et al
17188428	2007	Fusion genes in angiomatoid fibrous histiocytoma.	Hallor KH et al
10451705	1999	Prognostic impact of deletions at 1p36 and numerical aberrations in Ewing tumors.	Hattinger CM et al
15188455	2004	TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma.	Hisaoka M et al
15930281	2005	EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors.	Hu-Lieskovan S et al
16202544	2005	EWS-ETS oncoproteins: the linchpins of Ewing tumors.	Janknecht R et al
8963622	1996	An unusual cerebellar primitive neuroectodermal tumor with t(11;22) translocation: pathological and molecular analysis.	Jay V et al
20490326	2010	Ewing Sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions.	Jedlicka P et al
7700648	1995	A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.	Jeon IS et al
19859563	2009	GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors.	Joo J et al
9071576	1997	EWS-ERG fusion transcript produced by chromosomal insertion in a Ewing sarcoma.	Kaneko Y et al
8834175	1996	Fusion of an ETS-family gene, EIAF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy.	Kaneko Y et al
16537893	2006	Cooperative DNA binding with AP-1 proteins is required for transformation by EWS-Ets fusion proteins.	Kim S et al
19920188	2009	EWS/FLI and its downstream target NR0B1 interact directly to modulate transcription and oncogenesis in Ewing's sarcoma.	Kinsey M et al
11301318	2001	EWS/FLI alters 5'-splice site selection.	Knoop LL et al
8634690	1995	Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.	Labelle Y et al
8187063	1994	Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor.	Ladanyi M et al
16769671	2006	TLS, EWS and TAF15: a model for transcriptional integration of gene expression.	Law WJ et al
15917470	2005	Stimulation of Oct-4 activity by Ewing's sarcoma protein.	Lee J et al
19133275	2009	Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules.	Leemann-Zakaryan RP et al
12086853	2002	The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts.	Lessnick SL et al
17415412	2007	Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development.	Li H et al
18974141	2008	EWS-FLI1 induces developmental abnormalities and accelerates sarcoma formation in a transgenic mouse model.	Lin PP et al
10976720	2000	Soft tissue Ewing sarcoma--peripheral primitive neuroectodermal tumor with atypical clear cell pattern shows a new type of EWS-FEV fusion transcript.	Llombart-Bosch A et al
18525337	2008	Ewing sarcoma: historical perspectives, current state-of-the-art, and opportunities for targeted therapy in the future.	Ludwig JA et al
18295659	2008	Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversion-insertion mechanism of EWS-ERG fusion gene formation: a case analysis and literature review.	Maire G et al
11000339	2000	Detection of t(11;22)(q24;q12) translocation and EWS-FLI-1 fusion transcript in a case of solid pseudopapillary tumor of the pancreas.	Maitra A et al
12359745	2002	Recurrent rearrangement of the Ewing's sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia.	Martini A et al
10949935	2000	A novel zinc finger gene is fused to EWS in small round cell tumor.	Mastrangelo T et al
10366145	1999	Extraskeletal myxoid chondrosarcoma: a reappraisal of its morphologic spectrum and prognostic factors based on 117 cases.	Meis-Kindblom JM et al
10209495	1998	A novel EWS-ERG rearrangement generating two hybrid mRNAs in a peripheral primitive neuroectodermal tumour (pPNET) with a t(15;22) translocation.	Minoletti F et al
19247449	2009	EWS/ETS regulates the expression of the Dickkopf family in Ewing family tumor cells.	Miyagawa Y et al
18338330	2008	POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands.	Möller E et al
20019092	2010	The EWS/FLI1 oncogenic protein inhibits expression of the Wnt inhibitor DICKKOPF-1 gene and antagonizes beta-catenin/TCF-mediated transcription.	Navarro D et al
11854596	2002	Atypical pleomorphic extraosseous ewing tumor/peripheral primitive neuroectodermal tumor with unusual phenotypic/genotypic profile.	Navarro S et al
10221334	1999	Molecular characterization of the genomic breakpoint junction in a t(11;22) translocation in Ewing sarcoma.	Obata K et al
9706984	1998	Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript.	Ordi J et al
20231062	2010	Outcome and prognostic factors in olfactory neuroblastoma: a rare cancer network study.	Ozsahin M et al
7987849	1994	Characterization of the CHOP breakpoints and fusion transcripts in myxoid liposarcomas with the 12;16 translocation.	Panagopoulos I et al
9845364	1998	A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing.	Pellizzoni L et al
11406651	2001	A multiplex real-time pcr assay for the detection of gene fusions observed in solid tumors.	Peter M et al
8707406	1996	An EWS/ERG fusion with a truncated N-terminal domain of EWS in a Ewing's tumor.	Peter M et al
8307570	1993	Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation.	Plougastel B et al
12218455	2002	Fusion of the FUS and ATF1 genes in a large, deep-seated angiomatoid fibrous histiocytoma.	Raddaoui E et al
19289832	2009	EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.	Richter GH et al
20382729	2010	EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.	Riggi N et al
20197622	2010	CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis.	Rocchi A et al
19936782	2010	Soft tissue tumors associated with EWSR1 translocation.	Romeo S et al
18094413	2007	EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.	Rossi S et al
11289149	2001	The Ewing's sarcoma gene product functions as a transcriptional activator.	Rossow KL et al
10897036	2000	Identification of EWS/FLI-1 transcripts in giant-cell tumor of bone.	Scotlandi K et al
18666823	2009	Angiomatoid fibrous histiocytoma with t(2;22)(q33;q12.2) and EWSR1 gene rearrangement.	Shao L et al
12907633	2003	FUS/ERG gene fusions in Ewing's tumors.	Shing DC et al
19837262	2009	Fusion of EWSR1 with the DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma.	Sirvent N et al
10537274	1999	Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma.	Sjögren H et al
11156374	2000	Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21).	Sjögren H et al
16697960	2006	Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.	Smith R et al
20103643	2010	EWS/FLI1 oncogene activates caspase 3 transcription and triggers apoptosis in vivo.	Sohn EJ et al
16327442	2005	Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report.	Somers GR et al
8577710	1996	Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma.	Sorensen PH et al
12183411	2002	Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway.	Spahn L et al
19318479	2009	The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology.	Szuhai K et al
19783543	2009	The TET family of proteins: functions and roles in disease.	Tan AY et al
11441341	2001	Small round cell tumor with biphenotypic differentiation and variant of t(21;22)(q22;q12).	Tan SY et al
19801966	2010	Utility of FISH in the diagnosis of angiomatoid fibrous histiocytoma: a series of 18 cases.	Tanas MR et al
19122807	2008	TFIP11, CCNL1 and EWSR1 Protein-protein Interactions, and Their Nuclear Localization.	Tannukit S et al
7587112	1994	Genetic alterations in the chromosome 22q12 region associated with development of neuroectodermal tumors.	Thomas G et al
20596981	2009	Olfactory neuroblastoma.	Thompson LD et al
8644855	1996	Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types.	Thorner P et al
17482132	2007	Mesenchymal stem cell features of Ewing tumors.	Tirode F et al
16740692	2006	Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A.	Toretsky JA et al
9738976	1998	Molecular analysis of Ewing's sarcoma: another fusion gene, EWS-E1AF, available for diagnosis.	Urano F et al
17690209	2007	Undifferentiated small round cell sarcomas with rare EWS gene fusions: identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions.	Wang L et al
19561568	2009	Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts).	Wang WL et al
11063792	2000	Genetic characterization of angiomatoid fibrous histiocytoma identifies fusion of the FUS and ATF-1 genes induced by a chromosomal translocation involving bands 12q13 and 16p11.	Waters BL et al
15729702	2005	EWSR1 is fused to POU5F1 in a bone tumor with translocation t(6;22)(p21;q12).	Yamaguchi S et al
10982800	2000	EWS.Fli-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing.	Yang L et al
14597228	2003	The Ewing's sarcoma protein interacts with the Tudor domain of the survival motor neuron protein.	Young PJ et al
20222163	2010	Solid pseudopapillary tumor of the pancreas: a review of 553 cases in Chinese literature.	Yu PF et al
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11391597	2001	Acquisition of secondary structural chromosomal changes in pediatric ewing sarcoma is a probable prognostic factor for tumor response and clinical outcome.	Zielenska M et al
7958914	1994	A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP.	Zinszner H et al
7524604	1994	Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data.	Zoubek A et al
8401579	1993	EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts.	Zucman J et al
8223458	1993	Combinatorial generation of variable fusion proteins in the Ewing family of tumours.	Zucman J et al
11313995	2001	PDGF-C is an EWS/FLI induced transforming growth factor in Ewing family tumors.	Zwerner JP et al
9552022	1998	EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.	de Alava E et al

Other Information

Locus ID:

NCBI: 2130
MIM: 133450
HGNC: 3508
Ensembl: ENSG00000182944

Variants:

dbSNP: 2130
ClinVar: 2130
TCGA: ENSG00000182944
COSMIC: EWSR1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000182944	ENST00000331029	B0QYK0
ENSG00000182944	ENST00000332035	Q01844
ENSG00000182944	ENST00000332050	C9JGE3
ENSG00000182944	ENST00000333395	Q01844
ENSG00000182944	ENST00000360091	H7BY36
ENSG00000182944	ENST00000397938	Q01844
ENSG00000182944	ENST00000406548	Q01844
ENSG00000182944	ENST00000414183	Q01844
ENSG00000182944	ENST00000415761	B0QYJ6
ENSG00000182944	ENST00000436425	B0QYJ3
ENSG00000182944	ENST00000437155	F8WC90
ENSG00000182944	ENST00000444626	B0QYJ5
ENSG00000182944	ENST00000447973	B0QYJ4
ENSG00000182944	ENST00000455726	B0QYJ7
ENSG00000182944	ENST00000629659	A0A0D9SFL3

Expression (GTEx)

100

150

200

250

300

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title
38158126	2024	EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.
38168093	2024	Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.
38254207	2024	Report and literature review of four cases of EWSR1::NFATC2 round cell sarcoma.
38339014	2024	Identification of Novel/Rare EWSR1 Fusion Partners in Undifferentiated Mesenchymal Neoplasms.
38506112	2024	Endogenous EWSR1 Exists in Two Visual Modalities That Reflect Its Associations with Nucleic Acids and Concentration at Sites of Active Transcription.
38511874	2024	Ewing Sarcoma Related protein 1 recognizes R-loops by binding DNA forks.
38588409	2024	Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors.
38639853	2024	Central nervous system embryonal tumors with EWSR1-PLAGL1 rearrangements reclassified as INI-1 deficient tumors at relapse.
38158126	2024	EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.
38168093	2024	Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions.
38254207	2024	Report and literature review of four cases of EWSR1::NFATC2 round cell sarcoma.
38339014	2024	Identification of Novel/Rare EWSR1 Fusion Partners in Undifferentiated Mesenchymal Neoplasms.
38506112	2024	Endogenous EWSR1 Exists in Two Visual Modalities That Reflect Its Associations with Nucleic Acids and Concentration at Sites of Active Transcription.
38511874	2024	Ewing Sarcoma Related protein 1 recognizes R-loops by binding DNA forks.
38588409	2024	Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors.

Citation

Jean-Loup Huret

EWSR1 (Ewing sarcoma breakpoint region 1)

Atlas Genet Cytogenet Oncol Haematol. 2010-08-01

Online version: http://atlasgeneticsoncology.org/gene/85/gene-fusions-explorer/js/lib/tumors-explorer/

Historical Card

1998-04-01 EWSR1 (Ewing sarcoma breakpoint region 1) by Francine Mugneret Affiliation

Laboratoire de Cytogénétique, CHU Le Bocage, BP 77908, 21079 Dijon Cedex, France