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

Brain Tumor Pathology - Tập 32 - Trang 105-111 - 2014
David Cachia1, Khalida Wani2, Marta Penas-Prado1, Adriana Olar2, Ian E. McCutcheon3, Robert S. Benjamin4, Terri S. Armstrong1,5, Mark R. Gilbert1, Kenneth D. Aldape2
1Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
2Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA
3Department of Neuro-Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA
4Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
5Department of Family Health, The University of Texas Health Science Center School of Nursing, Houston, USA

Tóm tắt

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.

Tài liệu tham khảo

Hasselblatt M (2009) Ependymal tumors. Recent Results Cancer Res 171:51–66 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 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 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 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 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 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 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 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 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 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 Sugita Y, Terasaki M, Morioka M, Nakashima S, Nakamura Y, Ohshima K (2014) Ependymosarcoma with eosinophilic granular cells. Neuropathology 34:201–209 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 Reis RM, Konu-Lebleblicioglu D, Lopes JM, Kleihues P, Ohgaki H (2000) Genetic profile of gliosarcomas. Am J Pathol 156:425–432 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 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 Paulus W, Bayas A, Ott G, Roggendorf W (1994) Interphase cytogenetics of glioblastoma and gliosarcoma. Acta Neuropathol 88:420–425 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 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 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 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 Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454 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 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 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 Staudt LM (2010) Oncogenic activation of NF-kappaB. Cold Spring Harb Perspect Biol 2:a000109