- Human pathology

Home > A. Molecular pathology > EWSR1


MIM.133450 22q12

Saturday 15 November 2003


- Fusion genes in Ewing family tumors (EFTs)

EWSR1/FLI1 t(11;22)(q24;q12) EFT (Ewing Family Tumor)
ERG/EWSR1 t(21;22)(q22;q12) EFT (Ewing Family Tumor)
ETV1/EWSR1 t(7;22)(p22;q12) EFT (Ewing Family Tumor)
E1AF/EWSR1 t(17;22)(q12;q12) EFT (Ewing Family Tumor)
EWSR1/FEV t(2;22)(q13;q12) EFT (Ewing Family Tumor)
ETV4/EWSR1 t(17;22)(q12;q12) EFT (Ewing Family Tumor)
EWSR1/POU5F1 t(6;22)(p21;q12) EFT (Ewing Family Tumor) 18212089
EWSR1/SP3 fusion t(2;22)(q31;q12) EFT (Ewing Family Tumor) 17690209
EWSR1/ZNF278 22q12 rearrangement EFT (Ewing Family Tumor)

- Fusion genes in other tumors

ATF1/EWSR1 t(12;22)(q13;q12) malignant melanoma of soft parts (clear cell sarcoma)
EWSR1/TEC t(9;22)(q22;q12) extraskeletal myxoid chondrosarcoma
EWSR1/CHOP t(12;22)(q13;q12) myxoid liposarcoma
EWSR1/WT1 t(11;22) desmoplastic small round cell tumor (DSRCT)
EWSR1/SP3 fusion 2q31 and 22q12 undifferentiated small round cell sarcomas 17690209
EWSR1/ETV4 t(17;22)(q12;q12) undifferentiated sarcoma of infancy 8834175
EWSR1/ZNF384 (CIZ or NMP4) t(12;22)(p13;q12) acute myeloid leukemia 12359745
EWSR1/CREB1 t(2;22)(q33;q12) angiomatoid fibrous histiocytoma (AMFH) 17724745

- deletion of the 3’ EWSR1 gene in Ewing sarcoma with a t(21;22)(q22;q12) (15899394)

- EWSR1 Fusions With CREBs Family Transcription Factors ( ATF and CREB1 ) Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location. Kao YC, Sung YS, Zhang L, Chen CL, Vaiyapuri S, Rosenblum MK, Antonescu CR. Am J Surg Pathol. 2017 Apr;41(4):482-490. doi : 10.1097/PAS.0000000000000788
PMID: 28009602

Coupled alteration of transcription and splicing (18677114)

In cancer cells, gene expression is altered at the levels of transcription and mRNA maturation, with many splice variants being associated with cancer.

Splicing is tightly connected to transcription and can be affected by transcription elongation dynamics.

Moreover, various transcriptional coregulators that are altered in cancer, such as the proto-oncogene EWS, are thought to play a role in splicing. A recent study shows that an alteration of EWS in Ewing sarcoma alters the dynamics of RNA polymerase II over the CCND1 proto-oncogene encoding cyclin D1, leading to an increase in its transcription and to an alteration of splicing that results in high levels of the oncogenic cyclin D1b splice isoform.

The cyclin D1b isoform is highly expressed in Ewing sarcoma cells and tumors and stimulates Ewing sarcoma cell growth. Thus, alterations of transcriptional regulators in disease may lead to splicing alterations.


- TDP-43
- TAF15

Amyotrophic lateral sclerosis (ALS)

- EWSR1 variants in amyotrophic lateral sclerosis (ALS) (22454397)

  • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons.
  • Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15, have been connected to ALS.
  • These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo, and toxic effects when expressed in multiple model systems.
  • Three missense variants in EWSR1 have been identified in ALS patients, which were absent in a large number of healthy control individuals.
  • Disease-specific variants affect EWSR1 localization in motor neurons.
  • There are multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila.
  • Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1.
  • There is a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease.
  • This class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases.


- Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. (22454397)




- Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992;359:162-165.

- Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT. A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 1994;6:146-151.

- Owen LA, Lessnick SL. Identification of target genes in their native cellular context: an analysis of EWS/FLI in Ewing’s sarcoma. Cell Cycle 2006;5:2049-2053.

- Riggi N, Stamenkovic I. The biology of Ewing sarcoma. Cancer Lett 2007;254:1-10.

See also

- EWSR1/ETSs fusion proteins (16202544)


- EWSR1 Fusions With CREBs Family Transcription Factors ( ATF and CREB1 ) Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location. Kao YC, Sung YS, Zhang L, Chen CL, Vaiyapuri S, Rosenblum MK, Antonescu CR. Am J Surg Pathol. 2017 Apr;41(4):482-490. doi : 10.1097/PAS.0000000000000788 PMID: 28009602

- Wang L, Bhargava R, Zheng T, Wexler L, Collins MH, Roulston D, Ladanyi M. 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. J Mol Diagn. 2007 Sep;9(4):498-509. PMID: 17690209

- Antonescu CR, Dal Cin P, Nafa K, Teot LA, Surti U, Fletcher CD, Ladanyi M. EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2007 Aug 20; PMID: 17724745

- Janknecht R. EWS-ETS oncoproteins: the linchpins of Ewing tumors.
Gene. 2005 Dec 19;363:1-14. PMID: 16202544

- Li H, Watford W, Li C, Parmelee A, Bryant MA, Deng C, O’Shea J, Lee SB. Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest. 2007 May;117(5):1314-23. PMID: 17415412

- Hallor KH, Mertens F, Jin Y, Meis-Kindblom JM, Kindblom LG, Behrendtz M, Kalen A, Mandahl N, Panagopoulos I. Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer. 2005 Sep;44(1):97-102. PMID: 15884099

- Lee J, Hopcus-Niccum DJ, Mulvihill JJ, Li S. Cytogenetic and molecular cytogenetic studies of a variant of t(21;22), ins(22;21)(q12;q21q22), with a deletion of the 3’ EWSR1 gene in a patient with Ewing sarcoma. Cancer Genet Cytogenet. 2005 Jun;159(2):177-80. PMID: 15899394

- Martini A, La Starza R, Janssen H, Bilhou-Nabera C, Corveleyn A, Somers R, Aventin A, Foa R, Hagemeijer A, Mecucci C, Marynen P. Recurrent rearrangement of the Ewing’s sarcoma gene, EWSR1, or its homologue, TAF15, with the transcription factor CIZ/NMP4 in acute leukemia. Cancer Res. 2002 Oct 1;62(19):5408-12. PMID: 12359745