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Soft tissue tumors associated with EWSR1 translocation

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Abstract

The Ewing sarcoma breakpoint region 1 (EWSR1; also known as EWS) represents one of the most commonly involved genes in sarcoma translocations. In fact, it is involved in a broad variety of mesenchymal lesions which includes Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, clear cell sarcoma, angiomatoid fibrous histiocytoma, extraskeletal myxoid chondrosarcoma, and a subset of myxoid liposarcoma. The fusion products between EWSR1 and partners usually results in fusion of the N-terminal transcription-activating domain of EWSR1 and the C-terminal DNA-binding domain of the fusion partner, eventually generating novel transcription factors. EWSR1 rearrangement can be visualized by the means of fluorescence in situ hybridization (FISH). As soft tissue sarcomas represent a diagnostically challenging group, FISH analysis is an extremely useful confirmatory diagnostic tool. However, as in most instances a split-apart approach is used, the results of molecular genetics must be evaluated in context with morphology.

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References

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

    CAS  PubMed  Google Scholar 

  2. Zucman J, Delattre O, Desmaze C et al (1992) Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints. Genes Chromosomes Cancer 5:271–277

    CAS  PubMed  Google Scholar 

  3. Moller E, Stenman G, Mandahl N et al (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. J Pathol 215:78–86

    CAS  PubMed  Google Scholar 

  4. Plougastel B, Zucman J, Peter M et al (1993) Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation. Genomics 18:609–615

    CAS  PubMed  Google Scholar 

  5. Bovée JVMG, Devilee P, Cornelisse CJ et al (1995) Identification of an EWS-pseudogene using translocation detection by RT-PCR in Ewing's sarcoma. Biochem Biophys Res Commun 213:1051–1060

    PubMed  Google Scholar 

  6. Bertolotti A, Lutz Y, Heard DJ et al (1996) hTAF(II)68, a novel RNA/ssDNA-binding protein with homology to the pro-oncoproteins TLS/FUS and EWS is associated with both TFIID and RNA polymerase II. EMBO J 15:5022–5031

    CAS  PubMed  Google Scholar 

  7. Crozat A, Aman P, Mandahl P et al (1993) Fusion of CHOP a novel RNA-binding protein in human myxoid liposarcoma. Nature 363:640–644

    CAS  PubMed  Google Scholar 

  8. Morohoshi F, Arai K, Takahashi EI et al (1996) Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins. Genomics 38:51–57

    CAS  PubMed  Google Scholar 

  9. Azuma M, Embree LJ, Sabaawy H et al (2007) Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo. PLoS ONE 2:e979

    PubMed  Google Scholar 

  10. Stolow DT, Haynes SR (1995) Cabeza, a Drosophila gene encoding a novel RNA binding protein, shares homology with EWS and TLS, two genes involved in human sarcoma formation. Nucleic Acids Res 23:835–843

    CAS  PubMed  Google Scholar 

  11. Riggi N, Cironi L, Suva ML et al (2007) Sarcomas: genetics, signalling, and cellular origins. Part 1: the fellowship of TET. J Pathol 213:4–20

    CAS  PubMed  Google Scholar 

  12. Aman P, Panagopoulos I, Lassen C et al (1996) Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS. Genomics 37:1–8

    CAS  PubMed  Google Scholar 

  13. Zakaryan RP, Gehring H (2006) Identification and characterization of the nuclear localization/retention signal in the EWS proto-oncoprotein. J Mol Biol 363:27–38

    CAS  PubMed  Google Scholar 

  14. Bertolotti A, Melot T, Acker J et al (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. Mol Cell Biol 18:1489–1497

    CAS  PubMed  Google Scholar 

  15. Zhang D, Paley AJ, Childs G (1998) The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription. J Biol Chem 273:18086–18091

    CAS  PubMed  Google Scholar 

  16. Knoop LL, Baker SJ (2001) EWS/FLI alters 5′-splice site selection. J Biol Chem 276:22317–22322

    CAS  PubMed  Google Scholar 

  17. Knoop LL, Baker SJ (2000) The splicing factor U1C represses EWS/FLI-mediated transactivation. J Biol Chem 275:24865–24871

    CAS  PubMed  Google Scholar 

  18. Leemann-Zakaryan RP, Pahlich S, Sedda MJ et al (2009) Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules. J Mol Biol 386:1–13

    CAS  PubMed  Google Scholar 

  19. Li H, Watford W, Li C et al (2007) Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. J Clin Invest 117:1314–1323

    CAS  PubMed  Google Scholar 

  20. Thompson AD, Teitell MA, Arvand A et al (1999) Divergent Ewing's sarcoma EWS/ETS fusions confer a common tumorigenic phenotype on NIH3T3 cells. Oncogene 18:5506–5513

    CAS  PubMed  Google Scholar 

  21. May WA, Arvand A, Thompson AD et al (1997) EWS/FLI1-induced manic fringe renders NIH 3T3 cells tumorigenic. Nat Genet 17:495–497

    CAS  PubMed  Google Scholar 

  22. Ushigome S, Machinami R, Sorensen PH (2002) Ewing sarcoma/primitive neuroectodermal tumour (PNET). In: Fletcher CDM, Unni KK, Mertens F (eds) World Health Organization classification of tumours; pathology & genetics; tumours of soft tissue and bone. IARC Presss, Lyon, pp 298–300

    Google Scholar 

  23. Parham DM, Roloson GJ, Feely M et al (2001) Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center. Am J Surg Pathol 25:133–146

    CAS  PubMed  Google Scholar 

  24. Welsch T, Mechtersheimer G, Aulmann S et al (2006) Huge primitive neuroectodermal tumor of the pancreas: report of a case and review of the literature. World J Gastroenterol 12:6070–6073

    PubMed  Google Scholar 

  25. Dedeurwaerdere F, Giannini C, Sciot R et al (2002) Primary peripheral PNET/Ewing's sarcoma of the dura: a clinicopathologic entity distinct from central PNET. Mod Pathol 15:673–678

    PubMed  Google Scholar 

  26. Stout AP (1918) A tumor of the ulnar nerve. Proc N Y Pathol Soc 18:2–12

    Google Scholar 

  27. Askin FB, Rosai J, Sibley RK et al (1979) Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathologic entity of uncertain histogenesis. Cancer 43:2438–2451

    CAS  PubMed  Google Scholar 

  28. Ambros IM, Ambros PF, Strehl S et al (1991) MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors: evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration. Cancer 67:1886–1893

    CAS  PubMed  Google Scholar 

  29. Dei Tos AP, Wadden C, Calonje E et al (1995) Immunohistochemical demonstration of glycoprotein p30/32mic2 (CD99) in synovial sarcoma. Appl Immunohistochem 3:168–173

    CAS  Google Scholar 

  30. Terrier-Lacombe MJ, Guillou L, Chibon F et al (2009) Superficial primitive Ewing's sarcoma: a clinicopathologic and molecular cytogenetic analysis of 14 cases. Mod Pathol 22:87–94

    CAS  PubMed  Google Scholar 

  31. Hasegawa SL, Davison JM, Rutten A et al (1998) Primary cutaneous Ewing's sarcoma: immunophenotypic and molecular cytogenetic evaluation of five cases. Am J Surg Pathol 22:310–318

    CAS  PubMed  Google Scholar 

  32. Nicholson SA, McDermott MB, Swanson PE et al (2000) CD99 and cytokeratin-20 in small-cell and basaloid tumors of the skin. Appl Immunohistochem Mol Morphol 8:37–41

    CAS  PubMed  Google Scholar 

  33. Shing DC, McMullan DJ, Roberts P et al (2003) FUS/ERG gene fusions in Ewing's tumors. Cancer Res 63:4568–4576

    CAS  PubMed  Google Scholar 

  34. Ng TL, O'Sullivan MJ, Pallen CJ et al (2007) Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagnostics 9:459–463

    Google Scholar 

  35. Aurias A, Rimbaut C, Buffe D et al (1983) Chromosomal translocations in Ewing's sarcoma. Letter to the editor. N Engl J Med 309:496–498

    Google Scholar 

  36. Lessnick SL, Dacwag CS, Golub TR (2002) The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts. Cancer Cells 1:393–401

    CAS  Google Scholar 

  37. Kovar H (2005) Context matters: the hen or egg problem in Ewing's sarcoma. Semin Cancer Biol 15:189–196

    CAS  PubMed  Google Scholar 

  38. Serrano M, Lin AW, McCurrach ME et al (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602

    CAS  PubMed  Google Scholar 

  39. Riggi N, Cironi L, Provero P et al (2005) Development of Ewing's sarcoma from primary bone marrow-derived mesenchymal progenitor cells. Cancer Res 65:11459–11468

    CAS  PubMed  Google Scholar 

  40. Riggi N, Suva ML, Suva D et al (2008) EWS-FLI-1 expression triggers a Ewing's sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res 68:2176–2185

    CAS  PubMed  Google Scholar 

  41. Prieur A, Tirode F, Cohen P et al (2004) EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol 24:7275–7283

    CAS  PubMed  Google Scholar 

  42. Tirode F, Laud-Duval K, Prieur A et al (2007) Mesenchymal stem cell features of Ewing tumors. Cancer Cells 11:421–429

    CAS  Google Scholar 

  43. Szuhai K, Ijszenga M, Tanke HJ et al (2006) Molecular cytogenetic characterization of four previously established and two newly established Ewing sarcoma cell lines. Cancer Genet Cytogenet 166:173–179

    CAS  PubMed  Google Scholar 

  44. Szuhai K, Ijszenga M, De JD et al (2009) The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology. Clin Cancer Res 15:2259–2268

    CAS  PubMed  Google Scholar 

  45. Thorner P, Squire J, Chilton-MacNeill S et al (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. Am J Pathol 148:1125–1138

    CAS  PubMed  Google Scholar 

  46. Ed A, Kawai A, Healy JH et al (1998) EWS-FL11 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol 16:1248–1255

    Google Scholar 

  47. Mangham DC, Cannon A, Li XQ et al (1995) p53 overexpression in Ewing's sarcoma/primitive neuroectodermal tumour is an uncommon event. J Clin Pathol 48M:M79–M82

    Google Scholar 

  48. Ueda Y, Dockhorn-Dworniczak B, Blasius S et al (1993) Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone. J Cancer Res Clin Oncol 119:172–178

    CAS  PubMed  Google Scholar 

  49. Tsuchiya T, Sekine K, Hinohara S et al (2000) Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet 120:91–98

    CAS  PubMed  Google Scholar 

  50. Wei G, Antonescu CR, de Alava E et al (2000) Prognostic impact of INK4A deletion in Ewing sarcoma. Cancer 89:793–799

    CAS  PubMed  Google Scholar 

  51. Romeo S, Debiec-Rychter M, Van GM et al (2009) Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res 15:4191–4198

    CAS  PubMed  Google Scholar 

  52. Zogopoulos G, Teskey L, Sung L et al (2004) Ewing sarcoma: favourable results with combined modality therapy and conservative use of radiotherapy. Pediatr Blood Cancer 43:35–39

    PubMed  Google Scholar 

  53. Schmidt D, Herrmann C, Jürgens H et al (1991) Malignant peripheral neuroectodermal tumor and its necessary distinction from Ewing's sarcoma. A report from the Kiel Pediatric Tumor Registry. Cancer 68:2251–2259

    CAS  PubMed  Google Scholar 

  54. Parham DM, Hijazi Y, Steinberg SM et al (1999) Neuroectodermal differentiation in Ewing's sarcoma family of tumors does not predict tumor behavior. Hum Pathol 30:911–918

    CAS  PubMed  Google Scholar 

  55. Terrier Ph, Henry-Amar M, Triche TJ et al (1995) Is neuro-ectodermal differentiation of Ewing's sarcoma of bone associated with an unfavourable prognosis? Eur J Cancer 31A:307–314

    CAS  PubMed  Google Scholar 

  56. Toretsky JA, Kalebic T, Blakesley V et al (1997) The insulin-like growth factor-I receptor is required for EWS/FLI-1 transformation of fibroblasts. J Biol Chem 272:30822–30827

    CAS  PubMed  Google Scholar 

  57. Toretsky JA, Steinberg SM, Thakar M et al (2001) Insulin-like growth factor type 1 (IGF-1) and IGF binding protein-3 in patients with Ewing sarcoma family of tumors. Cancer 92:2941–2947

    CAS  PubMed  Google Scholar 

  58. Erkizan HV, Kong Y, Merchant M et al (2009) A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma. Nat Med 15:750–756

    CAS  PubMed  Google Scholar 

  59. Lessnick SL, Dei Tos AP, Sorensen PH et al (2009) Small round cell sarcomas. Semin Oncol 36:338–346

    CAS  PubMed  Google Scholar 

  60. Antonescu CR, Gerald W (2002) Desmoplastic small round cell tumour. In: Fletcher CDM, Unni KK, Mertens F (eds) World Health Organisation classification of tumours, pathology and genetics, tumours of soft tissue and bone. pp 216–218

  61. Parkash V, Gerald WL, Parma A et al (1995) Desmoplastic small round cell tumor of the pleura. Am J Surg Pathol 19:659–665

    CAS  PubMed  Google Scholar 

  62. Cummings OW, Ulbright TM, Young RH et al (1997) Desmoplastic small round cell tumors of the paratesticular region. A report of six cases. Am J Surg Pathol 21:219–225

    CAS  PubMed  Google Scholar 

  63. Wolf AN, Ladanyi M, Paull G et al (1999) The expanding clinical spectrum of desmoplastic small round-cell tumor: a report of two cases with molecular confirmation. Hum Pathol 30:430–435

    CAS  PubMed  Google Scholar 

  64. Tison V, Cerasoli S, Morigi F et al (1996) Intracranial desmoplastic small-cell tumor. Report of a case. Am J Surg Pathol 20:112–117

    CAS  PubMed  Google Scholar 

  65. Neder L, Scheithauer BW, Turel KE et al (2009) Desmoplastic small round cell tumor of the central nervous system: report of two cases and review of the literature. Virchows Arch 454:431–439

    PubMed  Google Scholar 

  66. Adsay V, Cheng J, Athanasian E et al (1999) Primary desmoplastic small cell tumor of soft tissues and bone of the hand. Am J Surg Pathol 23:1408–1413

    CAS  PubMed  Google Scholar 

  67. Hamazaki M, Okita H, Hata J et al (2006) Desmoplastic small cell tumor of soft tissue: molecular variant of EWS-WT1 chimeric fusion. Pathol Int 56:543–548

    PubMed  Google Scholar 

  68. Murphy AJ, Bishop K, Pereira C et al (2008) A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity. Hum Pathol 39:1763–1770

    CAS  PubMed  Google Scholar 

  69. Slomovitz BM, Girotra M, Aledo A et al (2000) Desmoplastic small round cell tumor with primary ovarian involvement: case report and review. Gynecol Oncol 79:124–128

    CAS  PubMed  Google Scholar 

  70. Bismar TA, Basturk O, Gerald WL et al (2004) Desmoplastic small cell tumor in the pancreas. Am J Surg Pathol 28:808–812

    PubMed  Google Scholar 

  71. Su MC, Jeng YM, Chu YC (2004) Desmoplastic small round cell tumor of the kidney. Am J Surg Pathol 28:1379–1383

    PubMed  Google Scholar 

  72. Wang LL, Perlman EJ, Vujanic GM et al (2007) Desmoplastic small round cell tumor of the kidney in childhood. Am J Surg Pathol 31:576–584

    PubMed  Google Scholar 

  73. Stuart-Buttle CE, Smart CJ, Pritchard S et al (2008) Desmoplastic small round cell tumour: a review of literature and treatment options. Surg Oncol 17:107–112

    CAS  PubMed  Google Scholar 

  74. Ordonez NG (1998) Desmoplastic small round cell tumor. I: a histopathologic study of 39 cases with emphasis on unusual histological patterns. Am J Surg Pathol 22:1303–1313

    CAS  PubMed  Google Scholar 

  75. Gerald WL, Miller HK, Battifora H et al (1991) Intra-abdominal desmoplastic small round-cell tumor. Report of 19 cases of a distinctive type of high-grade polyphenotypic malignancy affecting young individuals. Am J Surg Pathol 15:499–513

    CAS  PubMed  Google Scholar 

  76. Gerald WL, Ladanyi M, de Alava E et al (1998) Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol 16:3028–3036

    CAS  PubMed  Google Scholar 

  77. Ordonez NG (1998) Desmoplastic small round cell tumor. II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers. Am J Surg Pathol 22:1314–1327

    CAS  PubMed  Google Scholar 

  78. Lee SB, Kolquist KA, Nichols K et al (1997) The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. Na Genet 17:309–313

    CAS  Google Scholar 

  79. Werner H, Idelman G, Rubinstein M et al (2007) A novel EWS-WT1 gene fusion product in desmoplastic small round cell tumor is a potent transactivator of the insulin-like growth factor-I receptor (IGF-IR) gene. Cancer Lett 247:84–90

    CAS  PubMed  Google Scholar 

  80. Wong JC, Lee SB, Bell MD et al (2002) Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product. Oncogene 21:2009–2019

    CAS  PubMed  Google Scholar 

  81. Sawyer JR, Tryka AF, Lewis JM (1992) A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor. Am J Surg Pathol 16:411–416

    Article  CAS  PubMed  Google Scholar 

  82. Alaggio R, Rosolen A, Sartori F et al (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. Am J Surg Pathol 31:454–459

    PubMed  Google Scholar 

  83. Katz RL, Quezado M, Senderowicz AM et al (1997) An intra-abdominal small round cell neoplasm with features of primitive neuroectodermal and desmoplastic round cell tumor and a EWS/FLI-1 fusion transcript. Hum Pathol 28:502–509

    CAS  PubMed  Google Scholar 

  84. Li H, Smolen GA, Beers LF et al (2008) Adenosine transporter ENT4 is a direct target of EWS/WT1 translocation product and is highly expressed in desmoplastic small round cell tumor. PLoS ONE 3:e2353

    PubMed  Google Scholar 

  85. Antonescu CR, Nafa K, Segal NH et al (2006) EWS-CREB1: a recurrent variant fusion in clear cell sarcoma association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 12:5356–5362

    CAS  PubMed  Google Scholar 

  86. Zambrano E, Reyes-Mugica M, Franchi A et al (2003) An osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol 11:75–81

    PubMed  Google Scholar 

  87. Schaefer KL, Brachwitz K, Wai DH et al (2004) Expression profiling of t(12;22) positive clear cell sarcoma of soft tissue cell lines reveals characteristic up-regulation of potential new marker genes including ERBB3. Cancer Res 64:3395–3405

    CAS  PubMed  Google Scholar 

  88. Segal NH, Pavlidis P, Noble WS et al (2003) Classification of clear-cell sarcoma as a subtype of melanoma by genomic profiling. J Clin Oncol 21:1775–1781

    CAS  PubMed  Google Scholar 

  89. Langezaal SM, Graadt van Roggen JF, Cleton-Jansen AM et al (2001) Malignant melanoma is genetically distinct from clear cell sarcoma of tendons and aponeurosis (malignant melanoma of soft parts). Br J Cancer 84:535–538

    CAS  PubMed  Google Scholar 

  90. Graadt van Roggen JF, Mooi WJ, Hogendoorn PCW (1998) Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and cutaneous melanoma: exploring the histogenetic relationship between these two clinicopathological entities. J Pathol 186:3–7

    CAS  PubMed  Google Scholar 

  91. Antonescu CR, Tschernyavsky SJ, Woodruff JM et al (2002) Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagnostics 4:44–52

    CAS  Google Scholar 

  92. Zucman J, Delattre O, Desmaze C et al (1993) EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet 4:341–345

    CAS  PubMed  Google Scholar 

  93. Xie S, Price JE, Luca M et al (1997) Dominant-negative CREB inhibits tumor growth and metastasis of human melanoma cells. Oncogene 15:2069–2075

    CAS  PubMed  Google Scholar 

  94. Yokoyama S, Feige E, Poling LL et al (2008) Pharmacologic suppression of MITF expression via HDAC inhibitors in the melanocyte lineage. Pigment Cell Melanoma Res 21:457–463

    CAS  PubMed  Google Scholar 

  95. Lucas DR, Heim S (2002) Extraskeletal myxoid chondrosarcoma. In: Fletcher CDM, Unni KK, Mertens F (eds) Pathology & genetics. Tumours of soft tissue and bone. IARC Press, Lyon, pp 213–215

    Google Scholar 

  96. Aigner T, Oliveira AM, Nascimento AG (2004) Extraskeletal myxoid chondrosarcomas do not show a chondrocytic phenotype. Mod Pathol 17:214–221

    PubMed  Google Scholar 

  97. Subramanian S, West RB, Marinelli RJ et al (2005) The gene expression profile of extraskeletal myxoid chondrosarcoma. J Pathol 206:433–444

    CAS  PubMed  Google Scholar 

  98. Turc-Carel C, Dal Cin P, Rao U et al (1988) Recurrent breakpoints at 9q31 and 22q12.2 in extraskeletal myxoid chondrosarcoma. Cancer Genet Cytogenet 30:145–150

    CAS  PubMed  Google Scholar 

  99. Panagopoulos I, Mertens F, Isaksson M et al (2002) Molecular genetic characterization of the EWS/CHN and RBP56/CHN fusion genes in extraskeletal myxoid chondrosarcoma. Genes Chromosomes Cancer 35:340–352

    CAS  PubMed  Google Scholar 

  100. Filion C, Motoi T, Olshen AB et al (2009) The EWSR1/NR4A3 fusion protein of extraskeletal myxoid chondrosarcoma activates the PPARG nuclear receptor gene. J Pathol 217:83–93

    CAS  PubMed  Google Scholar 

  101. Fanburg-Smith JC, Dal Cin P (2002) Angiomatoid fibrous histiocytoma. In: Fletcher CDM, Unni KK, Mertens F (eds) World Health Organisation classification of tumours. Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon, pp 194–195

    Google Scholar 

  102. Rossi S, Szuhai K, Ijszenga M et al (2007) EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma. Clin Cancer Res 13:7322–7328

    CAS  PubMed  Google Scholar 

  103. Antonescu CR, Dal CP, Nafa K et al (2007) EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma. Genes Chromosomes Cancer 46:1051–1060

    CAS  PubMed  Google Scholar 

  104. Antonescu CR, Ladanyi M (2002) Myxoid Liposarcoma. In: Fletcher CDM, Unni KK, Mertens F (eds) World Health Organisation classification of tumours. Pathology and genetics of tumours of soft tissue and bone. IARC Press, Lyon, pp 40–43

    Google Scholar 

  105. Kilpatrick SE, Doyon J, Choong PFM et al (1996) The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases. Cancer 77:1450–1458

    CAS  PubMed  Google Scholar 

  106. Smith TA, Easley KA, Goldblum JR (1996) Myxoid/round cell liposarcoma of the extremities. A clinicopathologic study of 29 cases with particular attention to extent of round cell liposarcoma. Am J Surg Pathol 20:171–180

    CAS  PubMed  Google Scholar 

  107. Dei Tos AP, Wadden C, Fletcher CDM (1996) S-100 protein staining in liposarcoma. Its diagnostic utility in the high grade myxoid (round cell) variant. Appl Immunohistochem 4:95–101

    CAS  Google Scholar 

  108. Orvieto E, Furlanetto A, Laurino L et al (2001) Myxoid and round cell liposarcoma: a spectrum of myxoid adipocytic neoplasia. Semin Diagn Pathol 18:267–273

    CAS  PubMed  Google Scholar 

  109. Tallini G, Rosai J, Fletcher CDM et al (1995) Myxoid liposarcoma represents a distinct type of liposarcoma characterised by the specific cytogenetic translocation t(12; 16)(q13; p11). Mod Pathol 8

  110. Knight JC, Renwick PJ, Dal Cin P et al (1995) Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcma: molecular and cytogenetic analysis. Cancer Res 55:24–27

    CAS  PubMed  Google Scholar 

  111. Panagopoulos I, Hoglund M, Mertens F et al (1996) Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene 12:489–494

    CAS  PubMed  Google Scholar 

  112. Engstrom K, Willen H, Kabjorn-Gustafsson C et al (2006) The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells. Am J Pathol 168:1642–1653

    PubMed  Google Scholar 

  113. Antonescu CR, Tschernyavsky SJ, Decuseara R et al (2001) Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 7:3977–3987

    CAS  PubMed  Google Scholar 

  114. Schwab JH, Boland P, Guo T et al (2007) Skeletal metastases in myxoid liposarcoma: an unusual pattern of distant spread. Ann Surg Oncol 14:1507–1514

    PubMed  Google Scholar 

  115. Grosso F, Jones RL, Demetri GD et al (2007) Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study. Lancet Oncol 8:595–602

    CAS  PubMed  Google Scholar 

  116. Forni C, Minuzzo M, Virdis E et al (2009) Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther

  117. Lawrence B, Perez-Atayde A, Hibbard MK et al (2000) TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol 157:377–384

    CAS  PubMed  Google Scholar 

  118. Lamant L, Dastugue N, Pulford K et al (1999) A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 93:3088–3095

    CAS  PubMed  Google Scholar 

  119. Knezevich SR, McFadden DE, Tao W et al (1998) A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 18:184–187

    CAS  PubMed  Google Scholar 

  120. Knezevich SR, Garnett MJ, Pysher TJ et al (1998) ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res 58:5046–5048

    CAS  PubMed  Google Scholar 

  121. Tognon C, Knezevich SR, Huntsman D et al (2002) Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cells 2:367–376

    CAS  Google Scholar 

  122. Eguchi M, Eguchi-Ishimae M, Tojo A et al (1999) Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 93:1355–1363

    CAS  PubMed  Google Scholar 

  123. Argani P, Antonescu CR, Illei PB et al (2001) Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159:179–192

    CAS  PubMed  Google Scholar 

  124. Ladanyi M, Lui MY, Antonescu CR et al (2001) The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 20:48–57

    CAS  PubMed  Google Scholar 

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  1. Department of Pathology, General Hospital of Treviso, Piazza Ospedale 1, 31100, Treviso, Italy

    Salvatore Romeo & Angelo P. Dei Tos

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  1. Salvatore Romeo
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  2. Angelo P. Dei Tos
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Correspondence to Angelo P. Dei Tos.

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Romeo, S., Dei Tos, A.P. Soft tissue tumors associated with EWSR1 translocation. Virchows Arch 456, 219–234 (2010). https://doi.org/10.1007/s00428-009-0854-3

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