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Published in: Child's Nervous System 4/2019

01-04-2019 | Ependymoma | Case Report

A novel type of C11orf95-LOC-RELA fusion in a grade II supratentorial ependymoma: report of a case with literature review

Authors: Graziella Ribeiro de Sousa, Suely Kazue Nagahashi Marie, Sueli Mieko Oba-Shinjo, Leandra Náira Zambelli Ramalho, Luiz Gonzaga Tone, Elvis Terci Valera

Published in: Child's Nervous System | Issue 4/2019

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Abstract

Background

Ependymoma (EPN) is the third most common central nervous system tumor in childhood. Recent advances in the molecular classification of EPN revealed a supratentorial (ST) ependymoma subgroup characterized by C11orf95-RELA fusion.

Case Report

We describe a novel RELA-fusion composed by a chimeric transcript C11orf95-LOC-RELA in a supratentorial WHO grade II EPN occurring in a 4-year-old child. Metastatic loci at the brain, leptomeningeal involvement, and pulmonary nodules were identified at tumor recurrence. The child eventually died before 1 year after recurrence.

Conclusion

This index case showed aggressive behavior and nuclear accumulation of p65/RELA.
Literature
1.
go back to reference Ellisson DW, Kocak M, Figarella-Branger D, Giangaspero F, Chaterine G, Pietsch T, Frappaz D, Massimino M, Grill J, Boyett J, Grundy RG (2011) Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 10:7. https://doi.org/10.1186/1477-5751-10-7 CrossRef Ellisson DW, Kocak M, Figarella-Branger D, Giangaspero F, Chaterine G, Pietsch T, Frappaz D, Massimino M, Grill J, Boyett J, Grundy RG (2011) Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 10:7. https://​doi.​org/​10.​1186/​1477-5751-10-7 CrossRef
2.
go back to reference Figarella-Branger D, Lechapt-Zalcman E, Tabouret E, Jünger S, de Paula AM, Bouvier C, Colin C, Jouvet A, Forest F, Andreiuolo F, Quintin-Roue I, Machet MC, Heitzmann A, Milin S, Sevestre H, Godfraind C, Labrousse F, Metellus P, Scavarda D, Pietsch T (2016) Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling. Neuro-Oncology 18:919–927. https://doi.org/10.1093/neuonc/now025 CrossRefPubMedPubMedCentral Figarella-Branger D, Lechapt-Zalcman E, Tabouret E, Jünger S, de Paula AM, Bouvier C, Colin C, Jouvet A, Forest F, Andreiuolo F, Quintin-Roue I, Machet MC, Heitzmann A, Milin S, Sevestre H, Godfraind C, Labrousse F, Metellus P, Scavarda D, Pietsch T (2016) Supratentorial clear cell ependymomas with branching capillaries demonstrate characteristic clinicopathological features and pathological activation of nuclear factor-kappaB signaling. Neuro-Oncology 18:919–927. https://​doi.​org/​10.​1093/​neuonc/​now025 CrossRefPubMedPubMedCentral
3.
go back to reference Gessi M, Giagnacovo M, Modena P, Elefante G, Gianno F, Buttarelli FR, Arcella A, Donofrio V, Diomedi Camassei F, Nozza P, Morra I, Massimino M, Pollo B, Giangaspero F, Antonelli M (2017) Role of immunohistochemistry in the identification of supratentorial C11ORF95-RELA fused ependymoma in routine neuropathology. Am J Surg Pathol 43:56–63. https://doi.org/10.1097/pas.0000000000000979 CrossRef Gessi M, Giagnacovo M, Modena P, Elefante G, Gianno F, Buttarelli FR, Arcella A, Donofrio V, Diomedi Camassei F, Nozza P, Morra I, Massimino M, Pollo B, Giangaspero F, Antonelli M (2017) Role of immunohistochemistry in the identification of supratentorial C11ORF95-RELA fused ependymoma in routine neuropathology. Am J Surg Pathol 43:56–63. https://​doi.​org/​10.​1097/​pas.​0000000000000979​ CrossRef
7.
go back to reference Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger 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. https://doi.org/10.1038/nature13108 CrossRefPubMedPubMedCentral Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger 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. https://​doi.​org/​10.​1038/​nature13108 CrossRefPubMedPubMedCentral
12.
go back to reference Pagès M, Pajtler KW, Puget S, Castel D, Boddaert N, Tauziède-Espariat A, Picot S, Marie-Anne D, Kool M, Capper D, Sainte-Rose C, Fabrice C, Pfister SM, Pietsch T, Grill J, Varlet P, Andreiuolo F (2018) Diagnostics of paediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging. Brain Pathol. https://doi.org/10.1111/bpa.12664 Pagès M, Pajtler KW, Puget S, Castel D, Boddaert N, Tauziède-Espariat A, Picot S, Marie-Anne D, Kool M, Capper D, Sainte-Rose C, Fabrice C, Pfister SM, Pietsch T, Grill J, Varlet P, Andreiuolo F (2018) Diagnostics of paediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging. Brain Pathol. https://​doi.​org/​10.​1111/​bpa.​12664
13.
go back to reference Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728–743. https://doi.org/10.1016/j.ccell.2015.04.002 CrossRefPubMedPubMedCentral Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P, Reimand J, Warnatz HJ, Ryzhova M, Mack S, Ramaswamy V, Capper D, Schweizer L, Sieber L, Wittmann A, Huang Z, van Sluis P, Volckmann R, Koster J, Versteeg R, Fults D, Toledano H, Avigad S, Hoffman LM, Donson AM, Foreman N, Hewer E, Zitterbart K, Gilbert M, Armstrong TS, Gupta N, Allen JC, Karajannis MA, Zagzag D, Hasselblatt M, Kulozik AE, Witt O, Collins VP, von Hoff K, Rutkowski S, Pietsch T, Bader G, Yaspo ML, von Deimling A, Lichter P, Taylor MD, Gilbertson R, Ellison DW, Aldape K, Korshunov A, Kool M, Pfister SM (2015) Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728–743. https://​doi.​org/​10.​1016/​j.​ccell.​2015.​04.​002 CrossRefPubMedPubMedCentral
14.
go back to reference Pajtler KW, Mack SC, Ramaswamy V, Smith CA, Witt H, Smith A, Hansford JR, von Hoff K, Wright KD, Hwang E, Frappaz D, Kanemura Y, Massimino M, Faure-Conter C, Modena P, Tabori U, Warren KE, Holland E, Ichimura K, Giangaspero F, Castel D, von Deimling A, Kool M, Dirks PB, Grundy RG, Foreman N, Gajjar A, Korshunov A, Finlay J, Gilbertson R, Ellison DW, Aldape K, Merchant T, Bouffet E, Pfister SM, Taylor MD (2017) The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol 133:5–12. https://doi.org/10.1007/s00401-016-1643-0 CrossRefPubMed Pajtler KW, Mack SC, Ramaswamy V, Smith CA, Witt H, Smith A, Hansford JR, von Hoff K, Wright KD, Hwang E, Frappaz D, Kanemura Y, Massimino M, Faure-Conter C, Modena P, Tabori U, Warren KE, Holland E, Ichimura K, Giangaspero F, Castel D, von Deimling A, Kool M, Dirks PB, Grundy RG, Foreman N, Gajjar A, Korshunov A, Finlay J, Gilbertson R, Ellison DW, Aldape K, Merchant T, Bouffet E, Pfister SM, Taylor MD (2017) The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol 133:5–12. https://​doi.​org/​10.​1007/​s00401-016-1643-0 CrossRefPubMed
15.
go back to reference 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, 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. https://doi.org/10.1038/nature13109 CrossRefPubMedPubMedCentral 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, 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. https://​doi.​org/​10.​1038/​nature13109 CrossRefPubMedPubMedCentral
18.
go back to reference Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, Menon A, Jing X, Cao Q, Han B, Yu J, Wang L, Montie JE, Rubin MA, Pienta KJ, Roulston D, Shah RB, Varambally S, Mehra R, Chinnaiyan AM (2007) Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448:595–599 Tomlins SA, Laxman B, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, Menon A, Jing X, Cao Q, Han B, Yu J, Wang L, Montie JE, Rubin MA, Pienta KJ, Roulston D, Shah RB, Varambally S, Mehra R, Chinnaiyan AM (2007) Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature 448:595–599
19.
go back to reference Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M, Jones DT, Northcott PA, Garzia L, Bertrand KC, Wittmann A, Yao Y, Roberts SS, Massimi L, Van Meter T, Weiss WA, Gupta N, Grajkowska W, Lach B, Cho YJ, von Deimling A, Kulozik AE, Witt O, Bader GD, Hawkins CE, Tabori U, Guha A, Rutka JT, Lichter P, Korshunov A, Taylor MD, Pfister SM (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143–157. https://doi.org/10.1016/j.ccr.2011.07.007 CrossRefPubMedPubMedCentral Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M, Jones DT, Northcott PA, Garzia L, Bertrand KC, Wittmann A, Yao Y, Roberts SS, Massimi L, Van Meter T, Weiss WA, Gupta N, Grajkowska W, Lach B, Cho YJ, von Deimling A, Kulozik AE, Witt O, Bader GD, Hawkins CE, Tabori U, Guha A, Rutka JT, Lichter P, Korshunov A, Taylor MD, Pfister SM (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143–157. https://​doi.​org/​10.​1016/​j.​ccr.​2011.​07.​007 CrossRefPubMedPubMedCentral
Metadata
Title
A novel type of C11orf95-LOC-RELA fusion in a grade II supratentorial ependymoma: report of a case with literature review
Authors
Graziella Ribeiro de Sousa
Suely Kazue Nagahashi Marie
Sueli Mieko Oba-Shinjo
Leandra Náira Zambelli Ramalho
Luiz Gonzaga Tone
Elvis Terci Valera
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 4/2019
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-018-04028-5

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