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Soft tissue tumors: Ewing's tumors/Primitive neurectodermal tumors (PNET)

Identity

Phylum Soft Tissue Tumors:Uncertain differentiation:Ewing sarcoma / Primitive neurectodermal tumors (PNET)
Note Ewing tumours form a histologically heterogeneous family belonging to the group of small round-cell tumours and derived from neural crests cells.

Classification

    Ewing's tumors cover several distinct histological types:
  • peripheral neuroepithelioma
  • esthesioneuroblastoma
  • Askin's tumour
  • Ewing's sarcoma of bones and soft tissues
  • Clinics and Pathology

    Epidemiology peripheral neuroepithelioma is a very rare tumour (1% of all sarcomas); Ewing's sarcoma represents 5 to 15% of malignant bone and soft tissue tumours; two thirds of cases of Ewing's tumours occur before age 35 years, with a median age of 20 years.
    Clinics
  • peripheral neuroepithelioma typically occurs in the extremities (buttock and upper thigh, shoulder and upper arm);
  • esthesioneuroblastoma probably develops from the olfactive placode, in the nasal vault
  • Ewing's sarcoma of bones affects preferentially long bones (especially the femur), the pelvis, and the ribs; extraskeletal Ewing's sarcoma occur in the paravertebral region and chest wall, often in association with vertebrae and ribs, and in lower extremities
  • Askin's tumour is a paediatric tumour affecting mostly the chest wall and ribs
  •  
    Ewing's tumor : the tumor is composed of blastematous tissue with some differentiated glomerular structures associated with mesenchymal tissue and tubules. Courtesy Pierre Bedossa.
    Pathology
  • peripheral neuroepithelioma show sheets or lobules of small round-cells with a scarce cytoplasm; cells are often arranged in rosettes with a neurofibrillar center (Homer-Wright rosettes)
  • esthesioneuroblastoma is histologically very similar to neuroblastoma; rosettes may be present
  • Askin's tumour seems to be more related to neuroepithelioma than to Ewing's sarcoma
  • Ewing's sarcoma forms sheets of uniform small round-cells, sometimes arranged in a lobular pattern; the cytoplasm is scanty, pale stained and often vacuolated (glycogen); Ewing's sarcoma is considered as the less differentiated form of the Ewing's tumours family
  • Treatment the treatment of Ewing's tumours is generally based on combined therapy with adjuvant chemotherapy, surgical resection and radiotherapy.
    Prognosis combined therapies have largely improved the prognosis of Ewing's tumours in the recent years; the prognosis is mainly determined by the presence of metastases at the time of diagnosis (15 to 35% of the cases); the 5-year survival rate is 10-35% in patients with mestastases, and 54-74% for patients with a localised disease at presentation.

    Cytogenetics

    Cytogenetics
    Morphological
    about 90% of Ewing's tumours, whatever their type, show a t(11;22)(q24;q12); the translocation results in the fusion of the EWS gene with the transcription factor gene FLI1, leading to a hybrid transcript and an oncogenic chimeric protein; in about 5% of the cases, the EWS gene is involved in variant translocations: t(21;22)(q12;q12) and t(7;22)(p22;q12), leading to fusions EWS-ERG and EWS-ETV1, respectively.
    t(11;22)(q24;q12) in Ewing sarcoma, G- banding - top: courtesy Jean Luc Lai (with trisomy 8 on the right); - bottom: courtesy G. Reza Hafez, Eric B.Johnson, and Sara Morrison-Delap, UW Cytogenetic Services
    Cytogenetics Molecular additional anomalies in Ewing's tumours mainly consist in chromosome gains: +8 (45% of the cases) and, with a much lower frequency, trisomies 2, 5, 7, 9, 12 (between 10 and 15% of the cases); trisomy 1q, through unbalanced t(1q;16q), is observed in about 25% of the cases

    Genes involved and Proteins

    Gene Name EWSR1
    Location 22q12
    Protein RNA binding

    Gene Name FLI1
    Location 11q24

    Gene Name ERG
    Location 21q21

    Gene Name ETV1
    Location 7p22

    Result of the chromosomal anomaly

    Hybrid Gene
    Description the 5' EWSR1 is fused to parts of either FLI1, ERG, or ETV1
    Fusion Protein
    Description N terminal domain of EWS protein with DNA binding domain of FLI1, ERG (ETS family genes)
    Oncogenesis through transcription dysregulation
      

    Other genes implicated (Data extracted from papers in the Atlas)

    Genes APAF1 BCL11B CAV1 CD248 CITED2 ERG EWSR1 FGF2 FLI1 HSPB8
    KCMF1 NFATC2 NKX2-2 NPY1R NR0B1 PF4 POU4F1 PTCH1 PTPN13

    Translocations implicated (Data extracted from papers in the Atlas)

     inv(22)(q12q12) EWSR1/PATZ1
     t(11;22)(q24;q12) EWSR1/FLI1
     t(16;21)(p11;q22) FUS/ERG
     t(17;22)(q21;q12) EWSR1/ETV4
     t(2;16)(q35;p11) FUS/FEV
     t(2;22)(q36;q12) EWSR1/FEV
     t(20;22)(q13;q12) EWSR1/NFATC2
     t(21;22)(q21;q12) EWSR1/ERG
     t(7;22)(p22;q12) EWSR1/ETV1

    External links

    5230 Peripheral neuroepithelioma;Per neuro
    Mitelman databaseTopo ( Soft_tissue ) - Mitelman database (CGAP - NCBI)
    inv(22)(q12q12) - Mitelman database (CGAP - NCBI)
    t(11;22)(q24;q12) - Mitelman database (CGAP - NCBI)
    t(16;21)(p11;q22) - Mitelman database (CGAP - NCBI)
    t(17;22)(q21;q12) - Mitelman database (CGAP - NCBI)
    t(2;16)(q35;p11) - Mitelman database (CGAP - NCBI)
    t(2;22)(q36;q12) - Mitelman database (CGAP - NCBI)
    t(20;22)(q13;q12) - Mitelman database (CGAP - NCBI)
    t(21;22)(q21;q12) - Mitelman database (CGAP - NCBI)
    t(7;22)(p22;q12) - Mitelman database (CGAP - NCBI)
    COSMICHisto = - Site = soft_tissue fibrous_tissue_and_uncertain_origin (COSMIC)
    arrayMapTopo ( C49) Morph ( 8804/3 SARCOMA, NOS) - arrayMap (Zurich)

    Bibliography

    Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12).
    Turc-Carel C, Aurias A, Mugneret F, Lizard S, Sidaner I, Volk C, Thiery JP, Olschwang S, Philip I, Berger MP
    Cancer genetics and cytogenetics. 1988 ; 32 (2) : 229-238.
    PMID 3163261
     
    Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16).
    Mugneret F, Lizard S, Aurias A, Turc-Carel C
    Cancer genetics and cytogenetics. 1988 ; 32 (2) : 239-245.
    PMID 3163262
     
    Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors.
    Stephenson CF, Bridge JA, Sandberg AA
    Human pathology. 1992 ; 23 (11) : 1270-1277.
    PMID 1330877
     
    Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.
    Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G
    Nature. 1992 ; 359 (6391) : 162-165.
    PMID 1522903
     
    The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts.
    Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, Ambros PF, Sheer D, Turc-Carel C, Triche TJ
    The New England journal of medicine. 1994 ; 331 (5) : 294-299.
    PMID 8022439
     
    Soft tissue tumors.
    Enzinger FM, Weiss SW
    Soft tissue tumors..
     
    A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.
    Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN
    Oncogene. 1995 ; 10 (6) : 1229-1234.
    PMID 7700648
     
    -
    Forest M, Tomeno B, Vanel D
    Orthopedic surgical pathology, pp. 1944.
     
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written06-1998Jérôme Couturier

    Citation

    This paper should be referenced as such :
    Couturier, J
    Soft tissue tumors: Ewing's tumors
    Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):148-151.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Tumors/Ewing5010.html

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    indexed on : Sat Jul 26 14:21:13 CEST 2014


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