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C11orf95–RELA fusion present in a primary supratentorial ependymoma and recurrent sarcoma

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Abstract

Ependymomas are rare glial tumors of the central nervous system that arise from the cells lining the ventricles and central canal within the spinal cord. The distribution of these tumors along the neuroaxis varies by age, most commonly involving the spinal cord in adults and the posterior fossa in children. It is becoming evident that ependymomas of infratentorial, supratentorial, and spinal cord location are genetically distinct which may explain the differences in clinical outcomes. A novel oncogenic fusion involving the C11orf95 and RELA genes was recently described in supratentorial ependymomas that results in constitutive aberrant activation of the nuclear factor-kB signaling pathway. Ependymosarcomas are rare neoplasms in which a malignant mesenchymal component arises within an ependymoma. We here describe a case of a sarcoma developing in a patient previously treated with chemotherapy and radiation whose original ependymoma and recurrent sarcoma were both shown to carry the type 1 C11orf95–RELA fusion transcript indicating a monoclonal origin for both tumors.

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References

  1. Hasselblatt M (2009) Ependymal tumors. Recent Results Cancer Res 171:51–66

    Article  PubMed  Google Scholar 

  2. Johnson RA, Wright KD, Poppleton H, Mohankumar KM, Finkelstein D, Pounds SB, Rand V, Leary SE, White E, Eden C, Hogg T, Northcott P, Mack S, Neale G, Wang YD, Coyle B, Atkinson J, DeWire M, Kranenburg TA, Gillespie Y, Allen JC, Merchant T, Boop FA, Sanford RA, Gajjar A, Ellison DW, Taylor MD, Grundy RG, Gilbertson RJ (2010) Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466:632–636

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Wani K, Armstrong TS, Vera-Bolanos E, Raghunathan A, Ellison D, Gilbertson R, Vaillant B, Goldman S, Packer RJ, Fouladi M, Pollack I, Mikkelsen T, Prados M, Omuro A, Soffietti R, Ledoux A, Wilson C, Long L, Gilbert MR, Aldape K (2012) A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 123(5):727–738

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R, White E, Tang B, Orisme W, Gupta K, Rusch M, Chen X, Li Y, Nagahawhatte P, Hedlund E, Finkelstein D, Wu G, Shurtleff S, Easton J, Boggs K, Yergeau D, Vadodaria B, Mulder HL, Becksfort J, Gupta P, Huether R, Ma J, Song G, Gajjar A, Merchant T, Boop F, Smith AA, Ding L, Lu C, Ochoa K, Zhao D, Fulton RS, Fulton LL, Mardis ER, Wilson RK, Downing JR, Green DR, Zhang J, Ellison DW, Gilbertson RJ (2014) C11orf95–RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 506:451–455

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the US in 2006–2010. Neuro Oncol 15(Suppl 2):ii1–ii56

    Article  PubMed Central  PubMed  Google Scholar 

  6. Armstrong TS, Vera-Bolanos E, Gilbert MR (2011) Clinical course of adult patients with ependymoma: results of the Adult Ependymoma Outcomes Project. Cancer 117:5133–5141

    Article  PubMed  Google Scholar 

  7. Modena P, Lualdi E, Facchinetti F, Veltman J, Reid JF, Minardi S, Janssen I, Giangaspero F, Forni M, Finocchiaro G, Genitori L, Giordano F, Riccardi R, Schoenmakers EFPM, Massimino M, Sozzi G (2006) Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol 24:5223–5233

    Article  CAS  PubMed  Google Scholar 

  8. Puget S, Grill J, Valent A, Bieche I, Dantas-Barbosa C, Kauffmann A, Dessen P, Lacroix L, Geoerger B, Job B, Dirven C, Varlet P, Peyre M, Dirks PB, Sainte-Rose C, Vassal G (2009) Candidate genes on chromosome 9q33–34 involved in the progression of childhood ependymomas. J Clin Oncol 27:1884–1892

    Article  CAS  PubMed  Google Scholar 

  9. Witt H, Mack Stephen C, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M, Jones David TW, Northcott Paul A, Garzia L, Bertrand Kelsey C, Wittmann A, Yao Y, Roberts Stephen S, Massimi L, Van Meter T, Weiss William A, Gupta N, Grajkowska W, Lach B, Cho Y-J, von Deimling A, Kulozik Andreas E, Witt O, Bader Gary D, Hawkins Cynthia E, Tabori U, Guha A, Rutka James T, Lichter P, Korshunov A, Taylor Michael D, Pfister Stefan M (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143–157

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stutz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jager N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, Taylor MD (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445–450

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Rodriguez FJ, Scheithauer BW, Perry A, Oliveira AM, Jenkins RB, Oviedo A, Mork SJ, Palmer CA, Burger PC (2008) Ependymal tumors with sarcomatous change (“ependymosarcoma”): a clinicopathologic and molecular cytogenetic study. Am J Surg Pathol 32:699–709

    Article  PubMed  Google Scholar 

  12. Sugita Y, Terasaki M, Morioka M, Nakashima S, Nakamura Y, Ohshima K (2014) Ependymosarcoma with eosinophilic granular cells. Neuropathology 34:201–209

    Article  PubMed  Google Scholar 

  13. Feigin I, Allen LB, Lipkin L, Gross SW (1958) The endothelial hyperplasia of the cerebral blood vessels with brain tumors, and its sarcomatous transformation. Cancer 11:264–277

    Article  CAS  PubMed  Google Scholar 

  14. Reis RM, Konu-Lebleblicioglu D, Lopes JM, Kleihues P, Ohgaki H (2000) Genetic profile of gliosarcomas. Am J Pathol 156:425–432

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Boerman RH, Anderl K, Herath J, Borell T, Johnson N, Schaeffer-Klein J, Kirchhof A, Raap AK, Scheithauer BW, Jenkins RB (1996) The glial and mesenchymal elements of gliosarcomas share similar genetic alterations. J Neuropathol Exp Neurol 55:973–981

    Article  CAS  PubMed  Google Scholar 

  16. Actor B, Cobbers JM, Buschges R, Wolter M, Knobbe CB, Lichter P, Reifenberger G, Weber RG (2002) Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components. Genes Chromosomes Cancer 34:416–427

    Article  CAS  PubMed  Google Scholar 

  17. Paulus W, Bayas A, Ott G, Roggendorf W (1994) Interphase cytogenetics of glioblastoma and gliosarcoma. Acta Neuropathol 88:420–425

    Article  CAS  PubMed  Google Scholar 

  18. Horiguchi H, Hirose T, Kannuki S, Nagahiro S, Sano T (1998) Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study. Pathol Int 48:595–602

    Article  CAS  PubMed  Google Scholar 

  19. Biernat W, Aguzzi A, Sure U, Grant JW, Kleihues P, Hegi ME (1995) Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells. J Neuropathol Exp Neurol 54:651–656

    Article  CAS  PubMed  Google Scholar 

  20. Nagaishi M, Paulus W, Brokinkel B, Vital A, Tanaka Y, Nakazato Y, Giangaspero F, Ohgaki H (2012) Transcriptional factors for epithelial-mesenchymal transition are associated with mesenchymal differentiation in gliosarcoma. Brain Pathol 22:670–676

    Article  PubMed  Google Scholar 

  21. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  CAS  PubMed  Google Scholar 

  23. Zenali MJ, Zhang PL, Bendel AE, Brown RE (2009) Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in Ewing family of tumors. Ann Clin Lab Sci 39:160–166

    CAS  PubMed  Google Scholar 

  24. Sakakibara S, Espigol-Frigole G, Gasperini P, Uldrick TS, Yarchoan R, Tosato G (2013) A20/TNFAIP3 inhibits NF-kappaB activation induced by the Kaposi’s sarcoma-associated herpesvirus vFLIP oncoprotein. Oncogene 32:1223–1232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    Article  CAS  PubMed  Google Scholar 

  26. Staudt LM (2010) Oncogenic activation of NF-kappaB. Cold Spring Harb Perspect Biol 2:a000109

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

A Olar was supported by the National Institutes of Health/National Cancer Institute (Training Grant No. 5T32CA163185). K Aldape, K Wani, M Gilbert, and T Armstrong were supported by the CERN Foundation.

Conflict of interest

D Cachia, K Wani, M Penas Prado, A Olar, IE McCutcheon, RS Benjamin, KD Aldape report no disclosures. T.S. Armstrong serves as consultant for Immunocellular therapeutics; is on the advisory board for Roche; receives research support from Merck to Genentech. M.R. Gilbert reports research support from Genentech, Merck, Glaxo Smith Kline; receives honoraria from Merck, Genentech, AbbVie; and serves on the advisory board for Genetech, AbbVie, Heron Therapeutics.

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Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    David Cachia, Marta Penas-Prado, Terri S. Armstrong & Mark R. Gilbert

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Khalida Wani, Adriana Olar & Kenneth D. Aldape

  3. Department of Neuro-Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Ian E. McCutcheon

  4. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Robert S. Benjamin

  5. Department of Family Health, The University of Texas Health Science Center School of Nursing, 6901 Bertner Ave, Houston, TX, USA

    Terri S. Armstrong

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  1. David Cachia
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  2. Khalida Wani
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  3. Marta Penas-Prado
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  4. Adriana Olar
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  7. Terri S. Armstrong
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  8. Mark R. Gilbert
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  9. Kenneth D. Aldape
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Corresponding author

Correspondence to David Cachia.

Additional information

Dr. D. Cachia and Dr. K. Wani contributed equally to the preparation of this manuscript.

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Cachia, D., Wani, K., Penas-Prado, M. et al. C11orf95–RELA fusion present in a primary supratentorial ependymoma and recurrent sarcoma. Brain Tumor Pathol 32, 105–111 (2015). https://doi.org/10.1007/s10014-014-0205-1

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  • DOI: https://doi.org/10.1007/s10014-014-0205-1

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