Ewing's sarcoma and peripheral primitive neuroectodermal tumors after their genetic union

Current Opinion in Oncology

Volumn 10, Issue 4, 1998, Pages 334-342

  Kovar, Heinrich ^a  

^a ST ANNA CHILDREN S HOSPITAL   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR;

ARTICLE; CANCER GENETICS; EWING SARCOMA; FIBROBLAST; GENE REARRANGEMENT; HISTOLOGY; HUMAN; METASTASIS; MOLECULAR GENETICS; NEUROECTODERM TUMOR; NONHUMAN; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSGENE; TUMOR SUPPRESSOR GENE;

EID: 0031878238     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001622-199807000-00010     Document Type: Article

References (70)

1. Ambros IM, Ambros PF, Strehl S, Kovar H, Gadner H, Salzer Kuntschik M: 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 1991, 67:1886-1893.
2. Kovar H, Dworzak M, Strehl S, Schnell E, Ambros IM, Ambros PF, Gadner H: Overexpression of the pseudoautosomal gene MIC2 in Ewing's sarcoma and peripheral primitive neuroectodermal tumor. Oncogene 1990, 5:1067-1070.
3. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al.: The Ewing family of tumors - a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994, 331:294-299.
4. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, et al.: Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992, 359:162-165.
5. 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.
6. Zucman J, Melot T, Desmaze C, Ghysdael J, Plougastel B, Peter M, et al.: Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J 1993, 12:4481-4487.
7. Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN: A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 1995, 10:1229-1234.
8. Urano F, Umezawa A, Hong W, Kikuchi H, Hata J: A novel chimera gene between EWS and E1A-F, encoding the adenovirus E1A enhancer-binding protein, in extraosseous Ewing's sarcoma. Biochem Biophys Res Commun 1996, 219:608-612.
9. Kaneko Y, Yoshida K, Handa M, Toyoda Y, Nishihira H, Tanaka Y, et al.: Fusion of an ETS-family gene, EIAF, to EWS by t(17;22) (q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer 1996, 15:115-121.
10. Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H, Delattre O: A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 1997, 14:1159-1164. A novel EWS fusion partner from the ets transcription factor family is described.
11. Stiller CA, Parkin DM: Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull 1996, 52:682-703.
12. Zucman-Rossi J, Batzer MA, Stoneking M, Delattre O, Thomas G: Interethnic polymorphism of EWS intron 6: genome plasticity mediated by Alu retroposition and recombination. Hum Genet 1997, 99:357-363. The evolution of an AIu repeat region in EWS intron 6 is described that led to a polymorphism between populations of European and African origin, and may constitute the basis for interethnic differences in EFT incidence.
13. Panagopoulos I, Lassen C, Isaksson M, Mitelman F, Mandahl N, Aman P: Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia. Oncogene 1997, 15:1357-1362. This study is the first to describe recurrent sequence motifs in the vicinity of breakpoints in EWS family members and their fusion partners in myxoid liposarcoma and acute myeloid leukemia. In addition, nucleotide insertions of unknown origin were identified in two of the liposarcomas.
14. Bhagirath T, Abe S, Nojima T, Yoshida MC: Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma. Genes Chromosomes Cancer 1995, 13:126-132
15. Peter M, Mugneret F, Aunas A, Thomas G, Magdelenat H, Delattre O: An EWS/ERG fusion with a truncated N-terminal domain of EWS in a Ewing's tumor. Int J Cancer 1996, 67:339-342.
16. Liu J, Nau MM, Zucman-Rossi J, Powell JI, Allegra CJ, Wright JJ: LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor. Genes Chromosomes Cancer 1997, 18:232-239. Insertion at the translocation breakpoint in a desmoplastic small round cell tumor of a sequence homologous to a mobile element with an open reading frame potentially encoding a reverse transcriptase raises the intriguing possibility that retroposition could be involved in some EWS rearrangements.
17. Sorensen PH, Wu JK, Berean KW, Lim JF, Donn W, Frierson HF, et al.: Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma. Proc Natl Acad Sci U S A 1996, 93:1038-1043.
18. Sorensen PH, Shimada H, Liu XF, Lim JF, Thomas G, Triche TJ: Biphenotypic sarcomas with myogenic and neural differentiation express the Ewing's sarcoma EWS/FLI1 fusion gene. Cancer Res 1995, 55:1385-1392.
19. Marley EF, Liapis H, Humphrey PA, Nadler RB, Siegel CL, Zhu X, et al.: Primitive neuroectodermal tumor of the kidney-another enigma: a pathologic, immunohistochemical, and molecular diagnostic study. Am J Surg Pathol 1997, 21:354-359.
20. Quezado M, Benjamin DR, Tsokos M: EWS/FLI-1 fusion transcripts in three peripheral primitive neuroectodermal tumors of the kidney. Hum Pathol 1997, 28:767-771.
21. Sheaff M, McManus A, Scheimberg I, Paris A, Shipley J, Baithun S: Primitive neuroectodermal tumor of the kidney confirmed by fluorescence in situ hybridization. Am J Surg Pathol 1997, 21:461-468.
22. Burchill SA, Wheeldon J, Cullinane C, Lewis IJ: EWS-FLI1 fusion transcripts identified in patients with typical neuroblastoma. Eur J Cancer 1997, 33:239-243.
23. Desmaze C, Zucman J, Delattre O, Melot T, Thomas G, Aurias A: Interphase molecular cytogenetics of Ewing's sarcoma and peripheral neuroepithelioma t(11;22) with flanking and overlapping cosmid probes. Cancer Genet Cytogenet 1994, 74:13-18.
24. Yoshida H, Nagao K, Ito H, Yamamoto K, Ushigome S: Chromosomal translocations in human soft tissue sarcomas by interphase fluorescence in situ hybridization. Pathol Int 1997, 47:222-229.
25. Desmaze C, Brizard F, Turc-Carel C, Melot T, Delattre O, Thomas G, Aurias A: Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors. Cancer Genet Cytogenet 1997, 97:12-19.
26. Kaneko Y, Kobayashi H, Handa M, Satake N, Maseki N: EWS-ERG fusion transcript produced by chromosomal insertion in a Ewing sarcoma. Genes Chromosomes Cancer 1997, 18:228-231. In the absence of cytogenetic evidence for aberrations of chromosomes 21 and 22, comparison of RT-PCR and FISH data revealed insertion of a chromosomal fragment containing the EWS 5 portion into the ERG gene. Consequently, the chimeric EWS-ERG gene is expressed from chromosome 21.
27. Zinszner H, Albalat R, Ron D: A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev 1994, 8:2513-2526.
28. Meyer D, Wolff CM, Stiegler P, Senan F, Befort N, Befort JJ, Remy P: X1-fli, the Xenopus homologue of the fli-1 gene, is expressed during embryogenesis in a restricted pattern evocative of neural crest cell distribution. Mech Dev 1993, 44:109-121.
29. Dhordain P, Dewitte F, Desbiens X, Stehelin D, Duterque-Coquillaud M: Mesodermal expression of the chicken erg gene associated with precartilaginous condensation and cartilage differentiation. Mech Dev 1995, 50:17-28.
30. Chotteau-Lelievre A, Desbiens X, Pelczar H, Defossez PA, de Launoit Y: Differential expression patterns of the PEA3 group transcription factors through murine embryonic development. Oncogene 1997, 15:937-952. This is the first study on spatio-temporal embryonic expression in mammals of related ets oncogenes, which can be found as alternative EWS fusion partners in EFT.
31. Kovar H, Zoubek A, Gadner H: A long way from the definition of the molecular basis to benefit in the clinical management of Ewing tumours. Onkologie 1996, 19:234-240.
32. Kovar H: Progress in the molecular biology of Ewing tumors. Sarcoma 1998, in press.
33. Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A: SRE elements are binding sites for the fusion protein EWS-FLI-1. Nucleic Acids Res 1996, 24:1052-1058.
34. Watson DK, Robinson L, Hodge DR, Kola I, Papas TS, Seth A: FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1 a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements. Oncogene 1997, 14:213-221.
35. Braun BS, Frieden R, Lessnick SL, May WA, Denny CT: Identification of target genes for the Ewing's sarcoma EWS/FLI fusion protein by representational difference analysis. Mol Cell Biol 1995, 15:4623-4630.
36. Ben David Y, Giddens EB, Letwin K, Bernstein A: Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev 1991, 5:908-918.
37. Thompson AD, Braun BS, Arvand A, Stewart SD, May WA, Chen E, et al.: EAT-2 is a novel SH2 domain containing protein that is up regulated by Ewing's sarcoma EWS/FLI1 fusion gene. Oncogene 1996, 13:2649-2658.
38. May WA, Arvand A, Thompson AD, Braun BS, Wright M, Denny CT: EWS/FLI1-induced manic fringe renders NIH 3T3 cells tumorigenic. Nat Genet 1997, 17:495-497. The latest candidate EWS-FLI1-induced gene cloned by using RDA is described. Manic fringe encoding a signalling molecule, which is involved in somatic development, is differentially expressed in EWS-FLI1 and EWS-ERG versus FLI1 and EWS-ETV1 transfected NIH3T3 cells rendering them tumorigenic in SCID mice.
39. Johnston SH, Rauskolb C, Wilson R, Prabhakaran B, Irvine KD, Vogt TF: A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development 1997, 124:2245-2254.
40. Yuan YP, Schultz J, Mlodzik M, Bork P: Secreted fringe-like signaling molecules may be glycosyltransferases. Cell 1997, 88:9-11.
41. Toretsky JA, Kalebic T, Blakesley V, LeRoith D, Helman LJ: The insulin-like growth factor-I receptor is required for EWS/FLI-1 transformation of fibroblasts. J Biol Chem 1997, 272:30822-30827.
42. Kovar H, Aryee DN, Jug G, Henockl C, Schemper M, Delattre O, et al.: EWS/FLI-1 antagonists induce growth inhibition of Ewing tumor cells in vitro. Cell Growth Differ 1996, 7:429-437
43. Ouchida M, Ohno T, Fujimura Y, Rao VN, Reddy ES: Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene 1995, 11:1049-1054.
44. Toretsky JA, Connell Y, Neckers L, Bhat NK: Inhibition of EWS-FLI-1 fusion protein with antisense oligodeoxynucleotides. J Neurooncol 1997, 31:9-16.
45. Tanaka K, Iwakuma T, Hanmaya K, Sato H, Iwamoto Y: EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells. J Clin Invest 1997, 99:239-247. A quantitative RT-PCR approach is described that revealed genuine and antisense oligodeoxynucleotide-induced differences in EWS-FLI1 RNA abundancy paralleling proliferative activity of EFT cells in vitro.
46. Yi H, Fujimura Y, Ouchida M, Prasad DD, Rao VN, Reddy ES: Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. Oncogene 1997, 14:1259-1268.
47. Kovar H, Jug G, Aryee DNT, Zoubek A, Ambros P, Gruber B, et al.: Among genes involved in the RB-dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors. Oncogene 1997, 15:2225-2232. Loss of the tumor suppressor p76 in about one third of primary EFT and in more than 50% of EFT cell lines, mostly by homozygous deletion but also by mutation and by posttranscriptional mechanisms, is described. This aberration therefore constitutes the second most frequent genetic aberration in EFT characterized on the molecular level to date.
48. Kovar H, Auinger A, Jug G, Aryee D, Zoubek A, Salzer Kuntschik M, Gadner H: Narrow spectrum of infrequent p53 mutations and absence of MDM2 amplification in Ewing tumours. Oncogene 1993, 8:2683-2690.
49. Deloulme JC, Prichard L, Delattre O, Storm DR: The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. J Biol Chem 1997, 272:27369-27377. This report identifies the EWS gene product as a target of calcium signalling pathways regulating its RNA binding activity.
50. Bertolotti A, Melot T, Acker J, Vigneron M, Delattre O, Tora L: 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 Il complexes. Mol Cell Biol 1998, 78:7989-7997. By in vitro reconstitution experiments, the EWS protein is identified as a TATA box binding protein associated factor in the general transcription factor TFIID and in association with RNA polymerase II. Loss of its C-terminal domain, as is the case in the oncogenic fusion proteins, results in a switch of partner proteins and in loss from high molecular weight protein complexes.
51. Petermann R, Mossier BM, Aryee DNT, Khazak V, Golemis EA, Kovar H: Oncogenic EWS-FLi1 interacts with hsRPB7, a subunit of human RNA polymerase II. Oncogene 1998, in press. A bacterial sigma factor-like subunit of human RNA polymerase II, hsRPB7, is identified as an interacting protein for EWS-FLI1 in the yeast two-hybrid system, in vitro, and in EFT cells. The communication between these two proteins promoted transcriptional activation of ets responsive reporter genes.
52. Craft AW, Cotterill SJ, Bullimore JA, Pearson D: Long-term results from the first UKCCSG Ewing's Tumour Study (ET-1). United Kingdom Children's Cancer Study Group (UKCCSG) and the Medical Research Council Bone Sarcoma Working Party. Eur J Cancer 1997, 33:1061-1069. Long term survival figures for EFT patients in this study are based upon true data rather than extrapolated estimates because of the long follow-up (median, 11.2 years).
53. Verrill MW, Judson IR, Harmer CL, Fisher C, Thomas JM, Wiltshaw E: Ewing's sarcoma and primitive neuroectodermal tumor in adults: are they different from Ewing's sarcoma and primitive neuroectodermal tumor in children? J Clin Oncol 1997, 15:2611-2621. Clinical data for a group of 59 EFT patients ages 14 to 51 years are presented, revealing no difference in outcome to pediatric EFT.
54. Jurgens H, Exner U, Gadner H, Harms D, Michaelis J, Sauer R, et al.: Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial. Cancer 1988, 61:23-32.
55. Picci P, Bohling T, Bacci G, Ferrari S, Sangiorgi L, Mercuri M, et al.: Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities. J Clin Oncol 1997, 15:1553-1559. This is an update of a previous study by the authors confirming the prognostic impact of response to presurgical treatment in patients with localized disease treated with chemotherapy only. The validity of the relatively simple grading system proposed by the authors is impressively demonstrated.
56. Picci P, Rougraff BT, Bacci G, Neff JR, Sangiorgi L, Cazzola A, et al.: Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities. J Clin Oncol 1993, 11:1763-1769.
57. Ladenstein R, Philip T, Gardner H: Autologous stem cell transplantation for solid tumors in children. Curr Opin Pediatr 1997, 9:55-69.
58. Peter M, Magdelenat H, Michon J, Melot T, Oberlin O, Zucker JM, et al.: Sensitive detection of occult Ewing's cells by the reverse transcriptase-polymerase chain reaction. Br J Cancer 1995, 72:96-100.
59. Pfteiderer C, Zoubek A, Gruber B, Kronberger M, Ambras PF, Lion T, et al.: Detection of tumour cells in peripheral blood and bone marrow from Ewing tumour patients by RT-PCR. Int J Cancer 1995, 64:135-139.
60. Toretsky JA, Neckers L, Wexler LH: Detection of (11l22)(q24;q12) translocation-bearing cells in peripheral blood progenitor cells of patients with Ewing's sarcoma family of tumors. J Natl Cancer Inst 1995, 87:385-386
61. West DC, Grier HE, Swallow MM, Demetri GD, Granowetter L, Sklar J: Detection of circulating tumor cells in patients with Ewing's sarcoma and peripheral primitive neuroectodermal tumor. J Clin Oncol 1997, 15:583-588.
62. Zoubek A, Ladenstein R, Windhager R, Amann G, Fischmeister G, Kager L. et al.: Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT-PCR: a preliminary evaluation. Int J Cancer 1998, 79:56-60. After a number of similar studies have demonstrated the feasibility of using RT-PCR to detect minute amounts of tumor cells in blood or bone marrow, this is the first study discriminating between clinically distinct EFT subgroups. Data for bone marrow involvement are interpreted separately for patients with localized disease, patients with lung disease, and patients with bone metastases. After a median 2-year follow-up, no prognostic difference between bone marrow RT-PCR negative and positive cases could be identified, to date.
63. Zoubek A, Dockhorn Dworniczak B, Delattre O, Christiansen H, Niggli F, Gatterer Menz I, et al.: Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol 1996, 14:1245-1251.
64. De Alava E, Kawai A, Healey JH, Fligman I, Meyers P, Huvos AG, et al.: EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewings sarcoma. J Clin Oncol 1998, in press. By multivariate analysis, this study confirms earlier observations of a more favorable outcome for EFT patients with localized tumors expressing EWS-FLI1 type 1 transcripts. Importantly, these results appeared to be treatment-independent.
65. Mugneret F, Lizard S, Aurias A, Turc Carel C: Chromosomes in Ewing's sarcoma. II. Nonrandom additional changes, trisomy 8 and der(16)t(1;16). Cancer Genet Cytogenet 1988, 32:239-245.
66. Hattinger CM, Rumpler S, Ambros IM, Strehl S, Lion T, Zoubek A, et al.: Demonstration of the translocation der(16)t(1;16)(q12;q11.2) in interphase nuclei of Ewing tumors. Genes Chromosomes Cancer 1996, 17:141-150.
67. Douglass EC, Rowe ST, Valentine M, Parham D, Meyer WH, Thompson EI: A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor. Cytogenet Cell Genet 1990, 53:87-90.
68. Armengol G, Tarkkanen M, Virolainen M, Forus A, Valle J, Bohling T, et al.: Recurrent gams of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization. Br J Cancer 1997, 75:1403-1409.
69. Hamelin R, Zucman J, Melot T, Delattre O, Thomas G: p53 mutations in human tumors with chimeric EWS/FLI-1 genes. Int J Cancer 1994, 57:336-340.
70. Katz RL, Quezado M, Senderowicz AM, Villalba L, Laskin WB, Tsokos M: 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 1997, 28:502-509