Abstract
Ependymoma are primary tumors of the central nervous system (CNS) that typically arise from the wall of the cerebral ventricles or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based only on histologic features and clinical parameters is still difficult. Although numerous genetic abnormalities have been described, a reliable molecular prognostic marker is still not available due to the heterogeneity of this tumor group. In a microsatellite analysis we found frequent deletions in chromosomes 6, (particularly in the regions 6q15-q16, 6q21-q22.1, and 6q24.3-q25.3), in chromosome 9, (especially in 9p21 and 9q34) and in chromosome 22q (in the segment 22q11.21-q12.2 and 22q13.3).
The highest number of aberrations on chromosome 6 we found in a short segment of 6q25.3 containing the SNX9 and SYNJ2 genes and we could demonstrate a relation to a significant longer overall survival in paediatric patients. For chromosome 9 highly deleted was the region 9q31.3-33.2 containing the DCRI gene, which may play a role in the prognostic evaluation for ependymomas in adults. The chromosome 22 showed two ‘hot spots’: 22q11.21-q12.2 and 22q13.1-1-22q13.3. There was a significant association between aberrations and WHO grade of the tumor: grade II ependymomas showed significantly more aberrations than anaplastic ependymomas WHO grade III. The aim of these studies was to define characteristics genomic imbalances and to correlate them with clinical data in an attempt to describe aberrations with prognostic value in homogenously treated ependymoma patients.
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References
Beetz C, Brodoehl S, Patt S, Kalff R, Deufel T (2005) Low expression but infrequent genomic loss of the putative tumour suppressor DBCCR1 in astrocytoma. Oncol Rep 13:335–340
Carter M, Nicholson J, Ross F, Crolla J, Allibone R, Balaji V, Perry R, Walker D, Gilbertson R, Ellison DW (2002) Genetic abnormalities detected in ependymomas by comparative genomic hybridisation. Br J Cancer 86:929–939
Chuang YY, Tran NL, Rusk N, Nakada M, Berens ME, Symons M (2004) Role of synaptojanin 2 in glioma cell migration and invasion. Cancer Res 64:8271–8275
Ebert C, von Haken M, Meyer-Puttlitz B, Wiestler OD, Reifenberger G, Pietsch T, von Deimling A (1999) Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 155:627–632
Figarella-Branger D, Gambarelli D, Dollo C, Devictor B, Perez-Castillo AM, Genitori L, Lena G, Choux M, Pellissier JF (1991) Infratentorial ependymomas of childhood. Correlation between histological features, immunohistological phenotype, silver nucleolar organizer region staining values and post-operative survival in 16 cases. Acta Neuropathol 82:208–216
Figarella-Branger D, Civatte M, Bouvier-Labit C, Gouvernet J, Gambarelli D, Gentet JC, Lena G, Choux M, Pellissier JF (2000) Prognostic factors in intracranial ependymomas in children. J Neurosurg 93:605–613
Gilhuis HJ, van der Laak J, Wesseling P, Boerman RH, Beute G, Teepen JL, Grotenhuis JA, Kappelle AC (2004) Inverse correlation between genetic aberrations and malignancy grade in ependymal tumors: a paradox? J Neurooncol 66:111–116
Hirose Y, Aldape K, Bollen A, James CD, Brat D, Lamborn K, Berger M, Feuerstein BG (2001) Chromosomal abnormalities subdivide ependymal tumors into clinically relevant groups. Am J Pathol 158:1137–1143
Howard L, Nelson KK, Maciewicz RA, Blobel CP (1999) Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. J Biol Chem 274:31693–31699
Huang B, Starostik P, Kuhl J, Tonn JC, Roggendorf W (2002) Loss of heterozygosity on chromosome 22 in human ependymomas. Acta Neuropathol (Berl) 103:415–420
Huang B, Starostik P, Schraut H, Krauss J, Sorensen N, Roggendorf W (2003) Human ependymomas reveal frequent deletions on chromosomes 6 and 9. Acta Neuropathol (Berl) 106:357–362
Korshunov A, Golanov A, Sycheva R, Timirgaz V (2004) The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 100:1230–1237
Lewin B (2004) Genes VIII. Pearson Prentice Hall, Upper Saddle River
Lin Q, Lo CG, Cerione RA, Yang W (2002) The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation. J Biol Chem 277:10134–10138
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Lukashova VZI, Kneitz S, Monoranu CM, Rutkowski S, Hinkes B, Vince GH, Huang B, Roggendorf W (2007) Ependymoma gene expression profiles associated with histological subtype, proliferation, and patient survival. Acta Neuropathol (Berl) 113:325–337
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 EF, 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
Monoranu CM, Huang B, Zangen IL, Rutkowski S, Vince GH, Gerber NU, Puppe B, Roggendorf W (2008) Correlation between 6q25.3 deletion status and survival in pediatric intracranial ependymomas. Cancer Genet Cytogenet 182:18–26
Pezzolo A, Capra V, Raso A, Morandi F, Parodi F, Gambini C, Nozza P, Giangaspero F, Cama A, Pistoia V, Garre ML (2008) Identification of novel chromosomal abnormalities and prognostic cytogenetics markers in intracranial pediatric ependymoma. Cancer Lett 261:235–243
Pollack IF, Gerszten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, Janosky J, Deutsch M (1995) Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37:655–666, discussion 666–667
Reardon DA, Entrekin RE, Sublett J, Ragsdale S, Li H, Boyett J, Kepner JL, Look AT (1999) Chromosome arm 6q loss is the most common recurrent autosomal alteration detected in primary pediatric ependymoma. Genes Chromosomes Cancer 24:230–237
Reni M, Brandes AA, Vavassori V, Cavallo G, Casagrande F, Vastola F, Magli A, Franzin A, Basso U, Villa E (2004) A multicenter study of the prognosis and treatment of adult brain ependymal tumors. Cancer 100:1221–1229
Rickert CH (2004) Prognosis-related molecular markers in pediatric central nervous system tumors. J Neuropathol Exp Neurol 63:1211–1224
Rickert CH, Paulus W (2004) Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence. J Neuropathol Exp Neurol 63:399–417
Sambrook J, Fritsch FE, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Habor Press, New York
Schiffer D, Chio A, Giordana MT, Migheli A, Palma L, Pollo B, Soffietti R, Tribolo A (1991) Histologic prognostic factors in ependymoma. Childs Nerv Syst 7:177–182
Schneider D, Monoranu CM, Huang B, Rutkowski S, Gerber NU, Krauss J, Puppe B, Roggendorf W (2009) Pediatric supratentorial ependymomas show more frequent deletions on chromosome 9 than infratentorial ependymomas: a microsatellite analysis. Cancer Genet Cytogenet 191:90–96
Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P, Magdaleno S, Dalton J, Calabrese C, Board J, Macdonald T, Rutka J, Guha A, Gajjar A, Curran T, Gilbertson RJ (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335
Timmermann B, Kortmann RD, Kuhl J, Meisner C, Slavc I, Pietsch T, Bamberg M (2000) Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials HIT 88/89 and HIT 91. Int J Radiat Oncol Biol Phys 46:287–295
Timmermann B, Kortmann RD, Kuhl J, Rutkowski S, Dieckmann K, Meisner C, Bamberg M (2005) Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: results of the prospective German brain tumor trials HIT-SKK 87 and 92. Radiother Oncol 77:278–285
Wemmert S, Ketter R, Rahnenfuhrer J, Beerenwinkel N, Strowitzki M, Feiden W, Hartmann C, Lengauer T, Stockhammer F, Zang KD, Meese E, Steudel WI, von Deimling A, Urbschat S (2005) Patients with high-grade gliomas harboring deletions of chromosomes 9p and 10q benefit from temozolomide treatment. Neoplasia 7:883–893
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Monoranu, CM., Huang, B., Doreen, G. (2012). Ependymomas: Prognosis Based on Genetic Aberrations. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 8. Tumors of the Central Nervous System, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4213-0_27
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