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http://dx.doi.org/10.3340/jkns.2016.59.2.83

The Similarities and Differences between Intracranial and Spinal Ependymomas : A Review from a Genetic Research Perspective  

Lee, Chang-Hyun (Department of Neurosurgery, Ilsan Paik Hospital, Inje University College of Medicine)
Chung, Chun Kee (Department of Neurosurgery, Seoul National University Hospital)
Ohn, Jung Hun (Bioinformatics, Samsung Gene Institute, Samsung Medical Center)
Kim, Chi Heon (Department of Neurosurgery, Seoul National University Hospital)
Publication Information
Journal of Korean Neurosurgical Society / v.59, no.2, 2016 , pp. 83-90 More about this Journal
Abstract
Ependymomas occur in both the brain and spine. The prognosis of these tumors sometimes differs for different locations. The genetic landscape of ependymoma is very heterogeneous despite the similarity of histopathologic findings. In this review, we describe the genetic differences between spinal ependymomas and their intracranial counterparts to better understand their prognosis. From the literature review, many studies have reported that spinal cord ependymoma might be associated with NF2 mutation, NEFL overexpression, Merlin loss, and 9q gain. In myxopapillary ependymoma, NEFL and HOXB13 overexpression were reported to be associated. Prior studies have identified HIC-1 methylation, 4.1B deletion, and 4.1R loss as common features in intracranial ependymoma. Supratentorial ependymoma is usually characterized by NOTCH-1 mutation and p75 expression. TNC mutation, no hypermethylation of RASSF1A, and GFAP/NeuN expression may be diagnostic clues of posterior fossa ependymoma. Although MEN1, TP53, and PTEN mutations are rarely reported in ependymoma, they may be related to a poor prognosis, such as recurrence or metastasis. Spinal ependymoma has been found to be quite different from intracranial ependymoma in genetic studies, and the favorable prognosis in spinal ependymoma may be the result of the genetic differences. A more detailed understanding of these various genetic aberrations may enable the identification of more specific prognostic markers as well as the development of customized targeted therapies.
Keywords
Ependymoma; Genetics; NF2; Spinal; Intracranial;
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1 Magrassi L, Conti L, Lanterna A, Zuccato C, Marchionni M, Cassini P, et al. : Shc3 affects human high-grade astrocytomas survival. Oncogene 24 : 5198-5206, 2005   DOI
2 Magrassi L, Marziliano N, Inzani F, Cassini P, Chiaranda I, Skrap M, et al. : EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas. Cancer Lett 290 : 36-42, 2010   DOI
3 Modena P, Lualdi E, Facchinetti F, Veltman J, Reid JF, Minardi S, et al. : Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol 24 : 5223-5233, 2006   DOI
4 Monoranu CM, Huang B, Zangen IL, Rutkowski S, Vince GH, Gerber NU, et al. : Correlation between 6q25.3 deletion status and survival in pediatric intracranial ependymomas. Cancer Genet Cytogenet 182 : 18-26, 2008   DOI
5 Olsen TK, Gorunova L, Meling TR, Micci F, Scheie D, Due-Tonnessen B, et al. : Genomic characterization of ependymomas reveals 6q loss as the most common aberration. Oncol Rep 32 : 483-490, 2014   DOI
6 Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, et al. : Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27 : 728-743, 2015   DOI
7 Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li Y, et al. : C11orf95-RELA fusions drive oncogenic NF-${\kappa}B$ signalling in ependymoma. Nature 506 : 451-455, 2014   DOI
8 Rajaram V, Leuthardt EC, Singh PK, Ojemann JG, Brat DJ, Prayson RA, et al. : 9p21 and 13q14 dosages in ependymomas. A clinicopathologic study of 101 cases. Mod Pathol 17 : 9-14, 2004   DOI
9 Puget S, Grill J, Valent A, Bieche I, Dantas-Barbosa C, Kauffmann A, et al. : Candidate genes on chromosome 9q33-34 involved in the progression of childhood ependymomas. J Clin Oncol 27 : 1884-1892, 2009   DOI
10 Rajaram V, Gutmann DH, Prasad SK, Mansur DB, Perry A : Alterations of protein 4.1 family members in ependymomas : a study of 84 cases. Mod Pathol 18 : 991-997, 2005   DOI
11 Sherr CJ : The INK4a/ARF network in tumour suppression. Rev Mol Cell Biol 2 : 731-737, 2001   DOI
12 Reardon DA, Akabani G, Coleman RE, Friedman AH, Friedman HS, Herndon JE 2nd, et al. : Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors : phase II study results. J Clin Oncol 24 : 115-122, 2006   DOI
13 Rogers HA, Kilday JP, Mayne C, Ward J, Adamowicz-Brice M, Schwalbe EC, et al. : Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death. Acta Neuropathol 123 : 711-725, 2012   DOI
14 Rubio MP, Correa KM, Ramesh V, MacCollin MM, Jacoby LB, von Deimling A, et al. : Analysis of the neurofibromatosis 2 gene in human ependymomas and astrocytomas. Cancer Res 54 : 45-47, 1994
15 Scheil S, Bruderlein S, Eicker M, Herms J, Herold-Mende C, Steiner HH, et al. : Low frequency of chromosomal imbalances in anaplastic ependymomas as detected by comparative genomic hybridization. Brain Pathol 11 : 133-143, 2001
16 Schneider D, Monoranu CM, Huang B, Rutkowski S, Gerber NU, Krauss J, et al. : Pediatric supratentorial ependymomas show more frequent deletions on chromosome 9 than infratentorial ependymomas : a microsatellite analysis. Cancer Genet Cytogenet 191 : 90-96, 2009   DOI
17 Singh PK, Gutmann DH, Fuller CE, Newsham IF, Perry A : Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Mod Pathol 15 : 526-531, 2002   DOI
18 Suzuki SO, Iwaki T : Amplification and overexpression of mdm2 gene in ependymomas. Mod Pathol 13 : 548-553, 2000   DOI
19 Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, et al. : Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8 : 323-335, 2005   DOI
20 Teo C, Nakaji P, Symons P, Tobias V, Cohn R, Smee R : Ependymoma. Childs Nerv Syst 19 : 270-285, 2003   DOI
21 Barton VN, Donson AM, Kleinschmidt-DeMasters BK, Birks DK, Handler MH, Foreman NK : Unique molecular characteristics of pediatric myxopapillary ependymoma. Brain Pathol 20 : 560-570, 2010   DOI
22 Ahmad ZK, Brown CM, Cueva RA, Ryan AF, Doherty JK : ErbB expression, activation, and inhibition with lapatinib and tyrphostin (AG825) in human vestibular schwannomas. Otol Neurotol 32 : 841-847, 2011   DOI
23 Andreiuolo F, Puget S, Peyre M, Dantas-Barbosa C, Boddaert N, Philippe C, et al. : Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12 : 1126-1134, 2010   DOI
24 Athanasiou A, Perunovic B, Quilty RD, Gorgoulis VG, Kittas C, Love S : Expression of mos in ependymal gliomas. Am J Clin Pathol 120 : 699-705, 2003   DOI
25 Wang Z, Zhang J, Ye M, Zhu M, Zhang B, Roy M, et al. : Tumor suppressor role of protein 4.1B/DAL-1. Cell Mol Life Sci 71 : 4815-4830, 2014   DOI
26 Vera-Bolanos E, Aldape K, Yuan Y, Wu J, Wani K, Necesito-Reyes MJ, et al. : Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro Oncol 17 : 440-447, 2015   DOI
27 von Haken MS, White EC, Daneshvar-Shyesther L, Sih S, Choi E, Kalra R, et al. : Molecular genetic analysis of chromosome arm 17p and chromosome arm 22q DNA sequences in sporadic pediatric ependymomas. Genes Chromosomes Cancer 17 : 37-44, 1996   DOI
28 Waha A, Koch A, Hartmann W, Mack H, Schramm J, Sorensen N, et al. : Analysis of HIC-1 methylation and transcription in human ependymomas. Int J Cancer 110 : 542-549, 2004   DOI
29 Wani K, Armstrong TS, Vera-Bolanos E, Raghunathan A, Ellison D, Gilbertson R, et al. : A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 123 : 727-738, 2012   DOI
30 Ward S, Harding B, Wilkins P, Harkness W, Hayward R, Darling JL, et al. : Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma. Genes Chromosomes Cancer 32 : 59-66, 2001   DOI
31 Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, et al. : Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20 : 143-157, 2011   DOI
32 Yang I, Nagasawa DT, Kim W, Spasic M, Trang A, Lu DC, et al. : Chromosomal anomalies and prognostic markers for intracranial and spinal ependymomas. J Clin Neurosci 19 : 779-785, 2012   DOI
33 Zadnik PL, Gokaslan ZL, Burger PC, Bettegowda C : Spinal cord tumours : advances in genetics and their implications for treatment. Nat Rev Neurol 9 : 257-266, 2013
34 Fink KL, Rushing EJ, Schold SC Jr, Nisen PD : Infrequency of p53 gene mutations in ependymomas. J Neurooncol 27 : 111-115, 1996
35 Bettegowda C, Agrawal N, Jiao Y, Wang Y, Wood LD, Rodriguez FJ, et al. : Exomic sequencing of four rare central nervous system tumor types. Oncotarget 4 : 572-583, 2013   DOI
36 de Bont JM, Packer RJ, Michiels EM, den Boer ML, Pieters R : Biological background of pediatric medulloblastoma and ependymoma : a review from a translational research perspective. Neuro Oncol 10 : 1040-1060, 2008   DOI
37 Ebert C, von Haken M, Meyer-Puttlitz B, Wiestler OD, Reifenberger G, Pietsch T, et al. : Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 155 : 627-632, 1999   DOI
38 Garcia C, Gutmann DH : Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner. PLoS One 9 : e97320, 2014   DOI
39 Gilbertson RJ, Bentley L, Hernan R, Junttila TT, Frank AJ, Haapasalo H, et al. : ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin Cancer Res 8 : 3054-3064, 2002
40 Gonzalez-Gomez P, Bello MJ, Alonso ME, Arjona D, Lomas J, de Campos JM, et al. : CpG island methylation status and mutation analysis of the RB1 gene essential promoter region and protein-binding pocket domain in nervous system tumours. Br J Cancer 88 : 109-114, 2003   DOI
41 Gupta RK, Sharma MC, Suri V, Kakkar A, Singh M, Sarkar C : Study of chromosome 9q gain, Notch pathway regulators and Tenascin-C in ependymomas. J Neurooncol 116 : 267-274, 2014   DOI
42 Kilday JP, Rahman R, Dyer S, Ridley L, Lowe J, Coyle B, et al. : Pediatric ependymoma : biological perspectives. Mol Cancer Res 7 : 765-786, 2009   DOI
43 Zheng PP, Pang JC, Hui AB, Ng HK : Comparative genomic hybridization detects losses of chromosomes 22 and 16 as the most common recurrent genetic alterations in primary ependymomas. Cancer Genet Cytogenet 122 : 18-25, 2000   DOI
44 Zhou XP, Li YJ, Hoang-Xuan K, Laurent-Puig P, Mokhtari K, Longy M, et al. : Mutational analysis of the PTEN gene in gliomas : molecular and pathological correlations. Int J Cancer 84 : 150-154, 1999   DOI
45 Hagel C, Treszl A, Fehlert J, Harder J, von Haxthausen F, Kern M, et al. : Supra- and infratentorial pediatric ependymomas differ significantly in NeuN, p75 and GFAP expression. J Neurooncol 112 : 191-197, 2013   DOI
46 Hamilton DW, Lusher ME, Lindsey JC, Ellison DW, Clifford SC : Epigenetic inactivation of the RASSF1A tumour suppressor gene in ependymoma. Cancer Lett 227 : 75-81, 2005   DOI
47 Huang B, Starostik P, Kuhl J, Tonn JC, Roggendorf W : Loss of heterozygosity on chromosome 22 in human ependymomas. Acta Neuropathol 103 : 415-420, 2002   DOI
48 Huang B, Starostik P, Schraut H, Krauss J, Sorensen N, Roggendorf W : Human ependymomas reveal frequent deletions on chromosomes 6 and 9. Acta Neuropathol 106 : 357-362, 2003   DOI
49 Johnson RA, Wright KD, Poppleton H, Mohankumar KM, Finkelstein D, Pounds SB, et al. : Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466 : 632-636, 2010   DOI
50 Korshunov A, Witt H, Hielscher T, Benner A, Remke M, Ryzhova M, et al. : Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28 : 3182-3190, 2010   DOI
51 Kraus JA, de Millas W, Sorensen N, Herbold C, Schichor C, Tonn JC, et al. : Indications for a tumor suppressor gene at 22q11 involved in the pathogenesis of ependymal tumors and distinct from hSNF5/INI1. Acta Neuropathol 102 : 69-74, 2001
52 Lamszus K, Lachenmayer L, Heinemann U, Kluwe L, Finckh U, Hoppner W, et al. : Molecular genetic alterations on chromosomes 11 and 22 in ependymomas. Int J Cancer 91 : 803-808, 2001   DOI