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Molecular Characteristics of Pediatric Ependymomas: A Systematic Review

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Abstract

The prognosis for patients diagnosed with ependymoma is relatively poor, with a 5-year overall survival rate of 24–75%. Currently, tumors are treated by surgical resection followed by radiotherapy, as resection is the most consistent prognostic marker (up to 80%). Therefore, there is a pressing need to improve our understanding of the biology of these tumors and to develop new therapeutic targets. The present work was a systematic review of the current molecular knowledge of pediatric ependymomas. From January 2000 to December 2017, we carried out a search using “MeSH” (Medical Subject Heading), and “free-text” protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and EMBASE (OVID platform), combining the terms chromosomal alterations, genetic changes, epigenetic changes, and protein expression changes. We selected articles with samples from pediatric patients and chose publications with complete clinical features. Only 33 articles met the criteria for a meta-analysis, suggested by the state of methylation and expression of a characteristic marker of pediatric ependymomas. We found a chromosomal alteration and one gene associated with survival; these are candidates for bad prognosis biomarkers.

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References

  1. Ammerlaan ACJ, De Bustos C, Ararou A. Localization of a putative low-penetrance ependymoma susceptibility locus to 22q11 using a chromosome 22 tiling-path genomic microarray. Genes Chromosom Cancer. 2005;43:329–38.

    Article  CAS  Google Scholar 

  2. Rogers HA, Kilday JP, Mayne C. 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. 2012;123:711–25.

    Article  CAS  Google Scholar 

  3. Nambirajan A, Sharma MC, Gupta RK. Study of stem cell marker nestin and its correlation with vascular endothelial growth factor and microvascular density in ependymomas. Neuropathol Appl Neurobiol. 2014;40:714–25.

    Article  CAS  Google Scholar 

  4. Lukashova-v. Zangen I, Kneitz S, Monoranu CM. Ependymoma gene expression profiles associated with histological subtype, proliferation, and patient survival. Acta Neuropathol. 2007;113:325–37.

    Article  Google Scholar 

  5. Modena P, Buttarelli FR, Miceli R. Predictors of outcome in an AIEOP series of childhood ependymomas: a multifactorial analysis. 2012; 14: 1346–1356.

  6. Higgins JPT, Thompson SG, Deeks JJ. Measuring inconsistency in meta-analyses need for consistency, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC192859/pdf/3270557.pdf Accessed 28 June 2018.

  7. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  8. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  Google Scholar 

  9. Egger M, Smith GD, Schneider M. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  Google Scholar 

  10. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  Google Scholar 

  11. Suzuki SO, Iwaki T. Amplification and overexpression of mdm2 gene in ependymomas. Mod Pathol. 2000;13:548–53.

    Article  CAS  Google Scholar 

  12. Lamszus K, Lachenmayer L, Heinemann U. Molecular genetic alterations on chromosomes 11 and 22 in ependymomas. Int J Cancer. 2001;91:803–8.

    Article  CAS  Google Scholar 

  13. Hirose Y, Aldape K, Bollen A. Chromosomal abnormalities subdivide ependymal tumors into clinically relevant groups. Am J Pathol. 2001;158:1137–43.

    Article  CAS  Google Scholar 

  14. Ward S, Harding B, Wilkins P. Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma. Genes Chromosom Cancer. 2001;32:59–66.

    Article  CAS  Google Scholar 

  15. Dyer S, Prebble E, Davison V. Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups. Am J Pathol. 2002;161:2133–41.

    Article  CAS  Google Scholar 

  16. Gilbertson RJ, Bentley L, Hernan R. ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin Cancer Res. 2002;8:3054–64.

    CAS  PubMed  Google Scholar 

  17. Jeuken JWM, Sprenger SHE, Gilhuis J. Correlation between localization, age, and chromosomal imbalances in ependymal tumours as detected by CGH. J Pathol. 2002;197:238–44.

    Article  Google Scholar 

  18. Singh PK, Gutmann DH, Fuller CE. Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas. Mod Pathol. 2002;15:526–31.

    Article  Google Scholar 

  19. Zamecnik J, Snuderl M, Eckschlager T. Pediatric intracranial ependymomas: prognostic relevance of histological, immunohistochemical, and flow cytometric factors. Mod Pathol. 2003;16:980–91.

    Article  Google Scholar 

  20. Waha A, Koch A, Hartmann W. Analysis of HIC-1 methylation and transcription in human ependymomas. Int J Cancer. 2004;110:542–9.

    Article  CAS  Google Scholar 

  21. Tabori U, Ma J, Carter M. Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma. J Clin Oncol. 2006;24:1522–8.

    Article  CAS  Google Scholar 

  22. Karakoula K, Suarez-Merino B, Ward S. Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12–q13. Genes Chromosomes Cancer. 2008;47:1005–22.

    Article  CAS  Google Scholar 

  23. Monoranu CM, Huang B, Zangen IL Correlation between 6q25.3 deletion status and survival in pediatric intracranial ependymomas. Cancer Genet Cytogenet 2008; 182: 18–26.

    Article  CAS  Google Scholar 

  24. Pezzolo A, Capra V, Raso A. Identification of novel chromosomal abnormalities and prognostic cytogenetics markers in intracranial pediatric ependymoma. Cancer Lett. 2008;261:235–43.

    Article  CAS  Google Scholar 

  25. Rand V, Prebble E, Ridley L. Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma. Br J Cancer. 2008;99:1136–43.

    Article  CAS  Google Scholar 

  26. Snuderl M, Chi SN, De Santis SM. Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas. J Neuropathol Exp Neurol. 2008;67:911–20.

    Article  Google Scholar 

  27. Puget S, Grill J, Valent A. Candidate genes on chromosome 9q33–34 involved in the progression of childhood ependymomas. J Clin Oncol. 2009;27:1884–92.

    Article  CAS  Google Scholar 

  28. Rousseau A, Idbaih A, Ducray F. Specific chromosomal imbalances as detected by array CGH in ependymomas in association with tumor location, histological subtype and grade. J Neuro-Oncol. 2010;97:353–64.

    Article  Google Scholar 

  29. Andreiuolo F, Puget S, Peyre M. Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro-Oncology. 2010;12:1126–34.

    Article  CAS  Google Scholar 

  30. Korshunov A, Witt H, Hielscher T. Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol. 2010;28:3182–90.

    Article  Google Scholar 

  31. Alexiou GA, Stefanaki K, Moschovi M. Immunohistochemical expression of cell cycle/apoptosis regulators and epidermal growth factor receptor in pediatric intracranial ependymomas. J Child Neurol. 2011;26:195–8.

    Article  Google Scholar 

  32. Hagel C, Treszl A, Fehlert J. Supra- and infratentorial pediatric ependymomas differ significantly in NeuN, p75 and GFAP expression. J Neuro-Oncol. 2013;112:191–7.

    Article  CAS  Google Scholar 

  33. Moreno L, Popov S, Jury A. Role of platelet derived growth factor receptor (PDGFR) over-expression and angiogenesis in ependymoma. J Neuro-Oncol. 2013;111:169–76.

    Article  CAS  Google Scholar 

  34. Barszczyk M, Buczkowicz P, Castelo-Branco P, Mack SC, Ramaswamy V, Mangerel J, et al. Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells. Acta Neuropathol. 2014;128:863–77.

    Article  CAS  Google Scholar 

  35. Gupta RK, Sharma MC, Suri V. Study of chromosome 9q gain, Notch pathway regulators and tenascin-C in ependymomas. J Neuro-Oncol. 2014;116:267–74.

    Article  CAS  Google Scholar 

  36. Virág J, Kenessey I, Haberler C. Angiogenesis and angiogenic tyrosine kinase receptor expression in pediatric brain tumors. Pathol Oncol Res. 2014;20:417–26.

    Article  Google Scholar 

  37. Mack SC, Witt H, Piro RM. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature. 2014;506:445–50.

    Article  CAS  Google Scholar 

  38. Li AM, Dunham C, Tabori U. EZH2 expression is a prognostic factor in childhood intracranial ependymoma: a Canadian pediatric brain tumor consortium study. Cancer. 2015;121:1499–507.

    Article  CAS  Google Scholar 

  39. Araki A, Chocholous M, Gojo J. Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma. Acta Neuropathol Commun. 2016;4:88.

    Article  Google Scholar 

  40. Chen C, Chen L, Yao Y. Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: a multifactorial analysis of 176 patients. J Neuro-Oncol. 2016;127:43–52.

    Article  CAS  Google Scholar 

  41. Gojo J, Lötsch D, Spiegl-Kreinecker . Telomerase activation in posterior fossa group a ependymomas is associated with dismal prognosis and chromosome 1q gain. Neuro-Oncology 2017; 19: 1183–1194.

    Article  CAS  Google Scholar 

  42. Pajtler KW, Witt H, Sill M. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27:728–43.

    Article  CAS  Google Scholar 

  43. Cai C, Liu L, Shangguan H. Anti-oncogenic activity of Chibby in the development of human nasopharyngeal carcinoma. Oncol Lett. 2018:5849–58.

  44. Witt H, Mack SC, Ryzhova M. Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell. 2011;20:143–57.

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Acknowledgments

We thank the scholarship CVU 404762 granted from CONACYT and IMSS 011-2013 for the development of the student, and the postgrad program of Ciencias Biológicas, from the Universidad Nacional Autónoma de México. We thank the research scholarship of IMSS Foundation A. C. given to Dr. Normand García Hernández. We thank the given support to Dr. Fabio A. Salamanca Gómez from Hospital de Pediatría “Dr. Silvestre Frenk Freund,” IMSS.

Funding

We are grateful for the funding provided by the CONACYT Sectoral Funds S0008-2010-1, 142013. We thank the FIS IMSS for the support FIS/IMSS/PROT/949, 2009-785-042 and R-2014-785-094.

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Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Conceptualization by N.G.-H. and M.P.-R. Material preparation, data collection, and analysis were performed by M.P.-R., T.J.-C., A.G.-M., and N.G.-H. The first draft of the manuscript was written by M.P.-R. and T.J.-C., and all authors commented on previous versions of the manuscript. Supervision by N.G.-H. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Normand García-Hernández.

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Conflict of Interest

The authors declare that they have no competing interests.

Ethical Approval

The project was carried out under the authorization of the molecular biomarker search protocol for ependymal tumors in pediatric patients with registration number R-2014-785-094, at the Ethics Committee of National Ethics Commission from the Instituto Mexicano del Seguro Social, IMSS. All data have been kept in strict confidentiality.

Informed Consent

The tests were carried out following the rules established in the Helsinki agreement. All participants were duly informed and provided their written consent for each of the procedures.

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Pérez-Ramírez, M., Juárez-Cedillo, T., García-Méndez, A. et al. Molecular Characteristics of Pediatric Ependymomas: A Systematic Review. SN Compr. Clin. Med. 1, 861–868 (2019). https://doi.org/10.1007/s42399-019-00147-5

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