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Bone and Soft Tissue: Ewing-like sarcoma

Written2019-07Kelly M Bailey
University of Pittsburgh School of Medicine, Department of Pediatrics, Division of Pediatric Hematology/Oncology,

(Note : for Links provided by Atlas : click)


Abstract Ewing-like sarcoma is a recently defined subset of bone or soft tissue sarcomas. It is one of the pediatric small, round, blue cell tumors and is fusion gene-driven cancer. However, the driving fusions are distinct from that of the FET-ETS family rearrangements that define Ewing sarcoma (see separate entry for Ewing sarcoma).


ICD-Topo C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE
ICD-Morpho 9364/3 9260/3
Atlas_Id 6988
Phylum Soft Tissues::Ewing-like sarcoma
WHO/OMS Classification Soft Tissues
Other namesPreviously classified as Ewing tumors.


    Ewing-like sarcoma can arise in the bone or soft tissue.

Clinics and Pathology

Disease Ewing-like sarcoma
Etiology Ewing-like sarcomas are characterized by EWSR1/NFATC2 fusions, CIC fusions, or BCOR rearrangements.
Clinics Ewing-like sarcoma is a very rare subtype of bone, soft tissue or visceral sarcoma.
Pathology Small, round blue cells, with variable CD99 staining.
Treatment Patients with Ewing-like sarcoma are currently treated following Ewing sarcoma therapy protocols. This may change over time as more is understood about the individual fusions driving Ewing-like sarcomas.
Prognosis Survival is generally poorer for Ewing-like sarcomas compared to that of Ewing sarcoma. The exact prognoses for individual Ewing-like fusions types is still under investigation. In general, CIC-fused Ewing-like sarcomas have a very poor prognosis (<50%).


Note Ewing-like sarcomas harbor distinct fusions from that of Ewing sarcoma:
t(X;4)(p11.4; q31.1) BCOR/MALM3
t(X;22)(p11.4;q13.2) ZC3H7B/BCOR
t(X;4)(q13.1; q35.2) CIC/FOXO4
t(4;15)(q35.2; q14)CIC/NUTM1
t(4;19)(q35.2; q13.2)CIC/DUX4
t(20;22)(q13.2;q12.2) EWSR1/NFATC2
and fusion BCOR/CCNB3 (Xp11.4-Xp11.22)

Genes involved and Proteins

Note The following genes have been identified in Ewing-like sarcomas: EWSR1, NFATC2, BCOR, CCNB3, MAML3, CIC, DUX4, ZC3H7B, FOXO4, NUTM1
Gene NameEWSR1 (Ewing sarcoma breakpoint region 1)
Location 22q12.2
Protein Contains both a transcriptional activation domain and an RNA-binding domain.

Gene NameNFATC2 (Nuclear factor of activated T cells 2)
Location 20q13.2
Protein DNA binding protein, responsive to T-cell receptor signaling.

Gene NameBCOR (BCL6 corepressor)
Location Xp11.4
Protein Suppresses some genes by interacting with proteins comprising DNA binding complexes.

Gene NameMAML3 (Mastermind like transcriptional coactivator 3)
Location 4q31.1
Protein Involved in the NOTCH pathway.

Gene NameCCNB3 (Cyclin B3)
Location Xp11.22
Protein Cyclin family member; involved in cell cycle regulation.

Gene NameCIC (Capicua transcriptional repressor)
Location 19q13.2
Protein HMG-box family member.

Gene NameDUX4 (Double homeobox 4)
Location 4q35.2
Protein Associated with various forms of muscular dystrophy.

Gene NameZC3H7B (Zinc Finger CCCH-type containing 7B)
Location 22q13.2
Protein Nuclear protein; Contains domains involved in protein-protein and protein-nucleic acid interactions.

Gene NameFOXO4 (Forkhead Box O4)
Location Xq13.1
Protein Involved in cell growth and differentiation.

Gene NameNUTM1 (NUT midline carcinoma family member 1)
Location 15q14
Protein TERT expression regulation.

Result of the chromosomal anomaly

Fusion Protein


Sarcomas With CIC-rearrangements Are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases
Antonescu CR, Owosho AA, Zhang L, Chen S, Deniz K, Huryn JM, Kao YC, Huang SC, Singer S, Tap W, Schaefer IM, Fletcher CD
Am J Surg Pathol 2017 Jul;41(7):941-949
PMID 28346326
Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion: A Report of 2 Cases Showing Histologic Overlap With Clear Cell Sarcoma of Kidney, Suggesting Further Link Between BCOR-related Sarcomas of the Kidney and Soft Tissues
Argani P, Kao YC, Zhang L, Bacchi C, Matoso A, Alaggio R, Epstein JI, Antonescu CR
Am J Surg Pathol 2017 Dec;41(12):1702-1712
PMID 28817404
CIC-DUX4 fusion-positive round-cell sarcomas of soft tissue and bone: a single-institution morphological and molecular analysis of seven cases
Gambarotti M, Benini S, Gamberi G, Cocchi S, Palmerini E, Sbaraglia M, Donati D, Picci P, Vanel D, Ferrari S, Righi A, Dei Tos AP
Histopathology 2016 Oct;69(4):624-34
PMID 27079694
Ewing sarcoma
Grünewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de lava E, Kovar H, Sorensen PH, Delattre O, Dirksen U
Nat Rev Dis Primers 2018 Jul 5;4(1):5
PMID 29977059
BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas
Kao YC, Owosho AA, Sung YS, Zhang L, Fujisawa Y, Lee JC, Wexler L, Argani P, Swanson D, Dickson BC, Fletcher CDM, Antonescu CR
Am J Surg Pathol 2018 May;42(5):604-615
PMID 29300189
The second European interdisciplinary Ewing sarcoma research summit--A joint effort to deconstructing the multiple layers of a complex disease
Kovar H, Amatruda J, Brunet E, Burdach S, Cidre-Aranaz F, de Alava E, Dirksen U, van der Ent W, Grohar P, Grünewald TG, Helman L, Houghton P, Iljin K, Korsching E, Ladanyi M, Lawlor E, Lessnick S, Ludwig J, Meltzer P, Metzler M, Mora J, Moriggl R, Nakamura T, Papamarkou T, Radic Sarikas B, Rédini F, Richter GH, Rossig C, Schadler K, Schäfer BW, Scotlandi K, Sheffield NC, Shelat A, Snaar-Jagalska E, Sorensen P, Stegmaier K, Stewart E, Sweet-Cordero A, Szuhai K, Tirado OM, Tirode F, Toretsky J, Tsafou K, Üren A, Zinovyev A, Delattre O
Oncotarget 2016 Feb 23;7(8):8613-24
PMID 26802024
Ewing-like sarcoma: An emerging family of round cell sarcomas
Renzi S, Anderson ND, Light N, Gupta A
J Cell Physiol 2019 Jun;234(6):7999-8007
PMID 30257034
CIC-DUX4 Induces Small Round Cell Sarcomas Distinct from Ewing Sarcoma
Yoshimoto T, Tanaka M, Homme M, Yamazaki Y, Takazawa Y, Antonescu CR, Nakamura T
Cancer Res 2017 Jun 1;77(11):2927-2937
PMID 28404587


This paper should be referenced as such :
Kelly M Bailey
Bone and Soft Tissue: Ewing-like sarcoma
Atlas Genet Cytogenet Oncol Haematol. 2020;24(05):215-216.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(20;22)(q13.2;q12.2) EWSR1/NFATC2
 t(X;22)(p11.4;q13.2) ZC3H7B/BCOR
 t(X;4)(q13.1;q35.2) CIC/FOXO4

External links

Mitelman database t(20;22)(q13.2;q12.2) [CaseList]     t(20;22)(q13.2;q12.2) [Transloc - MCList]   EWSR1/NFATC2 Fusion - MCList]
Mitelman database t(20;22)(q13.2;q12.2) [CaseList]     t(20;22)(q13.2;q12.2) [Transloc - MCList]   EWSR1/NFATC2 Fusion - MCList]
Mitelman database t(X;22)(p11.4;q13.2) [CaseList]     t(X;22)(p11.4;q13.2) [Transloc - MCList]   ZC3H7B/BCOR Fusion - MCList]
Mitelman database t(X;22)(p11.4;q13.2) [CaseList]     t(X;22)(p11.4;q13.2) [Transloc - MCList]   ZC3H7B/BCOR Fusion - MCList]
Mitelman database t(X;22)(p11.4;q13.2) [CaseList]     t(X;22)(p11.4;q13.2) [Transloc - MCList]   ZC3H7B/BCOR Fusion - MCList]
Mitelman database t(X;4)(q13.1;q35.2) [CaseList]     t(X;4)(q13.1;q35.2) [Transloc - MCList]   CIC/FOXO4 Fusion - MCList]
arrayMap Topo ( C47,C49) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Disease databaseBone and Soft Tissue: Ewing-like sarcoma
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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indexed on : Tue Oct 12 14:40:18 CEST 2021

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