Skip to main content

Advertisement

Log in

ASPM gene expression in medulloblastoma

  • Original Paper
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19–20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features.

Methods

Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann–Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan–Meier test evaluated curve survival.

Results

All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters.

Conclusion

ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Bond J, Roberts E, Mochida GH, Hampshire DJ, Scott S, Askham JM, Springell K, Mahadevan M, Crow YJ, Markham AF, Walsh CA, Woods CG (2002) ASPM is a major determinant of cerebral cortical size. Nat Genet 32:316–320

    Article  CAS  PubMed  Google Scholar 

  2. Brinkley BR (2001) Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol 11:18–21

    Article  CAS  PubMed  Google Scholar 

  3. Chang CH, Housepian EM, Herbert C Jr (1969) An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93:1351–1359

    CAS  PubMed  Google Scholar 

  4. Fish JL, Kosodo Y, Enard W, Paabo S, Huttner WB (2006) Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc Natl Acad Sci USA 103:10438–10443

    Article  CAS  PubMed  Google Scholar 

  5. Guessous F, Li Y, Abounader R (2008) Signaling pathways in medulloblastoma. J Cell Physiol 217:577–583

    Article  CAS  PubMed  Google Scholar 

  6. Horvath S, Zhang B, Carlson M, Lu KV, Zhu S, Felciano RM, Laurance MF, Zhao W, Qi S, Chen Z, Lee Y, Scheck AC, Liau LM, Wu H, Geschwind DH, Febbo PG, Kornblum HI, Cloughesy TF, Nelson SF, Mischel PS (2006) Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc Natl Acad Sci USA 103:17402–17407

    Article  CAS  PubMed  Google Scholar 

  7. Korshunov A, Benner A, Remke M, Lichter P, von Deimling A, Pfister S (2008) Accumulation of genomic aberrations during clinical progression of medulloblastoma. Acta Neuropathol 116:383–390

    Article  CAS  PubMed  Google Scholar 

  8. Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki J, Mochida GH, Risinger JI, Goldsmith P, Gunsior M, Solomon G, Gersch W, Kim JH, Barrett JC, Walsh CA, Jurka J, Masumoto H, Larionov V (2005) The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genet 14:2155–2165

    Article  CAS  PubMed  Google Scholar 

  9. Lin SY, Pan HW, Liu SH, Jeng YM, Hu FC, Peng SY, Lai PL, Hsu HC (2008) ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma. Clin Cancer Res 14:4814–4820

    Article  CAS  PubMed  Google Scholar 

  10. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  11. MacDonald TJ (2008) Aggressive infantile embryonal tumors. J Child Neurol 23:1195–1204

    Article  PubMed  Google Scholar 

  12. Pizer B, Clifford S (2008) Medulloblastoma: new insights into biology and treatment. Arch Dis Child Educ Pract Ed 93:137–144

    Article  CAS  PubMed  Google Scholar 

  13. Rhoads A, Kenguele H (2005) Expression of IQ-motif genes in human cells and ASPM domain structure. Ethn Dis 15: S5-88-91

  14. Riparbelli MG, Callaini G, Glover DM, Avides Mdo C (2002) A requirement for the abnormal spindle protein to organise microtubules of the central spindle for cytokinesis in Drosophila. J Cell Sci 115:913–922

    CAS  PubMed  Google Scholar 

  15. Shimada M, Komatsu K (2009) Emerging connection between centrosome and DNA repair machinery. J Radiat Res (Tokyo) 50:295–301

    Article  CAS  Google Scholar 

  16. Wakefield JG, Bonaccorsi S, Gatti M (2001) The drosophila protein asp is involved in microtubule organization during spindle formation and cytokinesis. J Cell Biol 153:637–648

    Article  CAS  PubMed  Google Scholar 

Download references

Ackowledgments

This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC/UNIFESP).

It is declared in this work that there is no conflict of interest between the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sílvia Regina Caminada de Toledo.

Additional information

Financial and material support

GRAACC/CAPES/FAPESP N° 04/12133-6.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vulcani-Freitas, T.M., Saba-Silva, N., Cappellano, A. et al. ASPM gene expression in medulloblastoma. Childs Nerv Syst 27, 71–74 (2011). https://doi.org/10.1007/s00381-010-1252-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-010-1252-5

Keywords

Navigation