Distinct transcriptional signature and immunoprofile of CIC-DUX4 fusion-positive round cell tumors compared to EWSR1-rearranged ewing sarcomas: Further evidence toward distinct pathologic entities

Genes Chromosomes and Cancer

Volumn 53, Issue 7, 2014, Pages 622-633

  Specht, Katja ^a   Sung, Yun Shao ^b   Zhang, Lei ^b   Richter, Günther H S ^c   Fletcher, Christopher D ^d   Antonescu, Cristina R ^b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD99 ANTIGEN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ER81; TRANSCRIPTION FACTOR ERG; TRANSCRIPTION FACTOR ETS; TRANSCRIPTION FACTOR ETV4; TRANSCRIPTION FACTOR ETV5; TRANSCRIPTION FACTOR FLI 1; UNCLASSIFIED DRUG; WT1 PROTEIN; CALMODULIN BINDING PROTEIN; CIC-DUX4 FUSION PROTEIN, HUMAN; EWSR1 PROTEIN, HUMAN; ONCOPROTEIN; RNA BINDING PROTEIN; TRANSCRIPTOME;

ADOLESCENT; ADULT; ARTICLE; CHILD; CIC DUX4 FUSION GENE; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; EWING SARCOMA; EWSR1 ERG FUSION GENE; FEMALE; FUSION GENE; GENE EXPRESSION; GENE REARRANGEMENT; GENETIC TRANSCRIPTION; HUMAN; HUMAN TISSUE; IMMUNOGENETICS; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MICROSCOPY; MIDDLE AGED; MOLECULAR BIOLOGY; PATHOGENESIS; PRESCHOOL CHILD; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCHOOL CHILD; SMALL CELL SARCOMA; UPREGULATION; YOUNG ADULT; BONE TUMOR; GENE TRANSLOCATION; GENETICS; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

ADOLESCENT; ADULT; BONE NEOPLASMS; CALMODULIN-BINDING PROTEINS; CELL LINE, TUMOR; CHILD; FEMALE; GENE REARRANGEMENT; HUMANS; IMMUNOHISTOCHEMISTRY; MALE; MIDDLE AGED; ONCOGENE PROTEINS, FUSION; RNA-BINDING PROTEINS; SARCOMA, EWING; TRANSCRIPTION, GENETIC; TRANSCRIPTOME; TRANSLOCATION, GENETIC;

EID: 84899963751     PISSN: 10452257     EISSN: 10982264     Source Type: Journal    
DOI: 10.1002/gcc.22172     Document Type: Article

References (42)

1. Amin KM, Litzky LA, Smythe WR, Mooney AM, Morris JM, Mews DJ, Pass HI, Kari C, Rodeck U, Rauscher FJ, Kaiser LR, Albelda SM. 1995. Wilms' tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma. Am J Pathol 146:344-356.
2. Antonescu CR, Viale A, Sarran L, Tschernyavsky SJ, Gonen M, Segal NH, Maki RG, Socci ND, DeMatteo RP, Besmer P. 2004. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res 10:3282-3290.
3. Antonescu CR, Yoshida A, Guo T, Chang NE, Zhang L, Agaram NP, Qin LX, Brennan MF, Singer S, Maki RG. 2009. KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors. Cancer Res 69:7175-7179.
4. Barnoud R, Sabourin JC, Pasquier D, Ranchere D, Bailly C, Terrier-Lacombe MJ, Pasquier B. 2000. Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: A comparative study with other small round cell tumors. Am J Surg Pathol 24:830-836.
5. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW. 2011. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453-1455.
6. Charles AK, Moore IE, Berry PJ. 1997. Immunohistochemical detection of the Wilms' tumour gene WT1 in desmoplastic small round cell tumour. Histopathology 30:312-314.
7. Choi EY, Thomas DG, McHugh JB, Patel RM, Roulston D, Schuetze SM, Chugh R, Biermann JS, Lucas DR. 2013. Undifferentiated Small Round Cell Sarcoma With t(4;19)(q35;q13.1) CIC-DUX4 Fusion: A Novel Highly Aggressive Soft Tissue Tumor With Distinctive Histopathology. Am J Surg Pathol 37:1379-1386.
8. Dei Tos AP, Wadden C, Calonje E, Sciot R, Pauwels P, Knight JC, Dal Cin P, Fletcher CD. 1995. Immunohistochemical demonstration of gylcoprotein p30/32(MIC2) (CD99) in synovial sarcoma: a potential cause of diagnostic confusion. Appl Immunohistochem 3:168-173.
9. Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, Aurias A, Thomas G. 1992. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359:162-165.
10. Devaney K, Vinh TN, Sweet DE. 1993. Small cell osteosarcoma of bone: An immunohistochemical study with differential diagnostic considerations. Hum Pathol 24:1211-1225.
11. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (Eds): WHO Classification of Tumours of Soft Tissue and Bone, IARC: Lyon 2013.
12. Folpe AL, Hill CE, Parham DM, O'Shea PA, Weiss SW. 2000. Immunohistochemical detection of FLI-1 protein expression: A study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing's sarcoma/primitive neuroectodermal tumor. Am J Surg Pathol 24:1657-1662.
13. Graham C, Chilton-MacNeill S, Zielenska M, Somers GR. 2012. The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas. Hum Pathol 43:180-189.
14. Grubb GR, Yun K, Williams BR, Eccles MR, Reeve AE. 1994. Expression of WT1 protein in fetal kidneys and Wilms tumors. Lab Invest 71:472-479.
15. Hadju M, Singer S, Maki RG, Schwartz G, Keohan M, Antonescu CR. 2010. IGF2 over-expression in solitary fibrous tumours is independent of anatomical location and is related to loss of imprinting. J Pathol 221:300-307.
16. Hancock JD, Lessnick SL. 2008. A transcriptional profiling meta-analysis reveals a core EWS-FLI gene expression signature. Cell Cycle 7:250-256.
17. Hauer K, Calzada-Wack J, Steiger K, Grunewald TG, Baumhoer D, Plehm S, Buch T, Prazeres da Costa O, Esposito I, Burdach S, Richter GH. 2013. DKK2 mediates osteolysis, invasiveness, and metastatic spread in Ewing sarcoma. Cancer Res 73:967-977.
18. Italiano A, Sung YS, Zhang L, Singer S, Maki RG, Coindre JM, Antonescu CR. 2012. High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. Genes Chromosomes Cancer 51:207-218.
19. Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN. 1995. A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene 10:1229-1234.
20. Jimenez G, Guichet A, Ephrussi A, Casanova J. 2000. Relief of gene repression by torso RTK signaling: Role of capicua in Drosophila terminal and dorsoventral patterning. Genes Dev 14:224-231.
21. Kawamura-Saito M, Yamazaki Y, Kaneko K, Kawaguchi N, Kanda H, Mukai H, Gotoh T, Motoi T, Fukayama M, Aburatani H, Takizawa T, Nakamura T. 2006. Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation. Hum Mol Genet 15:2125-2137.
22. Ng TL, O'Sullivan MJ, Pallen CJ, Hayes M, Clarkson PW, Winstanley M, Sorensen PH, Nielsen TO, Horsman DE. 2007. Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV. J Mol Diagn 9:459-463.
23. 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.
24. Peter M, Couturier J, Pacquement H, Michon J, Thomas G, Magdelenat H, Delattre O. 1997. A new member of the ETS family fused to EWS in Ewing tumors. Oncogene 14:1159-1164.
25. Rakheja D, Goldman S, Wilson KS, Lenarsky C, Weinthal J, Schultz RA. 2008. Translocation (4;19)(q35;q13.1)-associated primitive round cell sarcoma: Report of a case and review of the literature. Pediatr Dev Pathol 11:239-244.
26. Richkind KE, Romansky SG, Finklestein JZ. 1996. t(4;19)(q35;q13.1): a recurrent change in primitive mesenchymal tumors? Cancer Genet Cytogenet 87:71-74.
27. Richter GH, Plehm S, Fasan A, Rossler S, Unland R, Bennani-Baiti IM, Hotfilder M, Lowel D, von Luettichau I, Mossbrugger I, Quintanilla-Martinez L, Kovar H, Staege MS, Muller-Tidow C, Burdach S. 2009. EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation. Proc Natl Acad Sci USA 106:5324-5329.
28. Riopel M, Dickman PS, Link MP, Perlman EJ. 1994. MIC2 analysis in pediatric lymphomas and leukemias. Hum Pathol 25:396-399.
29. Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W, Herold-Mende C, von Deimling A, Hartmann C. 2012. CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta Neuropathol 123:853-860.
30. Sankar S, Lessnick SL. 2011. Promiscuous partnerships in Ewing's sarcoma. Cancer Genet 204:351-365.
31. Segal NH, Pavlidis P, Antonescu CR, Maki RG, Noble WS, DeSantis D, Woodruff JM, Lewis JJ, Brennan MF, Houghton AN, Cordon-Cardo C. 2003. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am J Pathol 163:691-700.
32. Shing DC, McMullan DJ, Roberts P, Smith K, Chin SF, Nicholson J, Tillman RM, Ramani P, Cullinane C, Coleman N. 2003. FUS/ERG gene fusions in Ewing's tumors. Cancer Res 63:4568-4576.
33. Somers GR, Shago M, Zielenska M, Chan HS, Ngan BY. 2004. Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: case report. Pediatr Dev Pathol 7:538-545.
34. Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT. 1994. A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 6:146-151.
35. Stevenson AJ, Chatten J, Bertoni F, Miettinen M. 1994. CD99 (p30/32MIC2) neuroectodermal/Ewing's sarcoma antigen as an immunohistochemical marker: Review of more than 600 tumors and the literature experience. Appl Immunohistochem 2:231-240.
36. Urano F, Umezawa A, Hong W, Kikuchi H, Hata J. 1996. 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 219:608-612.
37. van der Maarel SM, Tawil R, Tapscott SJ. 2011. Facioscapulohumeral muscular dystrophy and DUX4: Breaking the silence. Trends Mol Med 17:252-258.
38. Wang X, Cairns MJ. 2013. Gene set enrichment analysis of RNA-Seq data: integrating differential expression and splicing. BMC Bioinformatics 14 Suppl 5:S16.
39. Wang L, Bhargava R, Zheng T, Wexler L, Collins MH, Roulston D, Ladanyi M. 2007. 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 9:498-509.
40. Wang WL, Patel NR, Caragea M, Hogendoorn PC, Lopez-Terrada D, Hornick JL, Lazar AJ. 2012. Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma. Mod Pathol 25:1378-1383.
41. Yoshimoto M, Graham C, Chilton-MacNeill S, Lee E, Shago M, Squire J, Zielenska M, Somers GR. 2009. Detailed cytogenetic and array analysis of pediatric primitive sarcomas reveals a recurrent CIC-DUX4 fusion gene event. Cancer Genet Cytogenet 195:1-11.
42. Zucman J, Melot T, Desmaze C, Ghysdael J, Plougastel B, Peter M, Zucker JM, Triche TJ, Sheer D, Turc-Carel C, et al. 1993. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. Embo J 12:4481-4487.