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Analysis of different medulloblastoma histotypes by two-dimensional gel and MALDI-TOF

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Abstract

Objective

The purpose of this study is to detect different protein profiles in medulloblastoma (MDB) that may be clinically relevant and to check the correspondence of histological classification of MDB with proteomic profiles.

Materials and methods

Surgical specimens, snap frozen at the time of neurosurgery, entered the proteomic study. Eight samples from patients (age range, 4 months–26 years) with different MDB histotypes (five classic, one desmoplastic/nodular, one with extensive nodularity, and one anaplastic) were analyzed by two-dimensional gel electrophoresis. One sample for each histotype was further characterized by matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis.

Results

Eighty-six unique proteins were identified and compared to histology, with the determination of proteins expressed by single histotypes and of a smaller number of proteins shared by two or three histotypes. The sharp difference of protein expression was found to be in agreement with WHO histological classification, with the identification of type-specific proteins with limited overlapping between histotypes.

Conclusion

Proteomic analysis confirmed and strengthened the difference between histotypes as biologically relevant. Cluster analysis enhanced the distance of extensive nodularity MDB from other histotypes. Possible innovative approaches to therapy may rely upon a proteomic-based classification of MDB tightly correlated to histology. The utility of snap freezing tumoral samples must be stressed and should become a mandatory task for pathologists.

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References

  1. Giangaspero F, Eberhart CG, Haapsalo H, Pietsch T, Wiestler O, Ellison DW (2007) Medulloblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of central nervous system. IARC Press, Lyon, pp 132–140

    Google Scholar 

  2. Gilbertson RJ, Gajjar A (2005) Molecular biology of medulloblastoma: will it ever make a difference to clinical management? J Neurooncol 75:273–278

    Article  PubMed  CAS  Google Scholar 

  3. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J (2005) Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 352:978–986

    Article  PubMed  CAS  Google Scholar 

  4. Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ (2006) Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol 7:813–820

    Article  PubMed  Google Scholar 

  5. Kool M, Koster J, Bunt J Hasselt NE, Lakeman A, van Sluis P, Troost D, Meeteren NS, Caron HN, Cloos J, Mrsić A, Ylstra B, Grajkowska W, Hartmann W, Pietsch T, Ellison D, Clifford SC, Versteeg R (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One 3:e3088

    Article  PubMed  Google Scholar 

  6. Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, Zhao W, Nicholson SL, Taylor RE, Bailey S, Clifford SC (2011) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical, pathologic, and molecular variables. J Clin Oncol 29(11):1400–1407

    Article  PubMed  Google Scholar 

  7. Rutkowski S, von Hoff K, Emser A, Zwiener I, Pietsch T, Figarella-Branger D, Giangaspero F, Ellison DW, Garre ML, Biassoni V, Grundy RG, Finlay JL, Dhall G, Raquin MA, Grill J (2010) Survival and prognostic factors of early childhood medulloblastoma: an international meta-analysis. J Clin Oncol 28(33):4961–4968

    Article  PubMed  Google Scholar 

  8. Barbero G, Carta F, Giribaldi G, Mandili G, Crobu S, Ceruti C, Fontana D, Destefanis P, Turrini F (2006) Protein/RNA coextraction and small two-dimensional polyacrylamide gel electrophoresis for proteomic/gene expression analysis of renal cancer biopsies. Anal Biochem 349:62–71

    Article  PubMed  CAS  Google Scholar 

  9. Development Core Team (2009) R: a Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. http://www.R-project.org

  10. Bolker B, Bonebakker L, Gentleman R, Huber W, Liaw A, Lumley. T, Maechler M, Magnusson A, Moeller S, Schwartz M, Venables B (2010) gplots: Various R programming tools for plotting data. R package version 2.8.0. http://CRAN.R-project.org/package=gplots

  11. Polans AS, Witkowska D, Haley TL, Amundson D, Baizer L, Adamus G (1995) Recoverin, a photoreceptor-specific calcium-binding protein, is expressed by the tumor of a patient with cancer-associated retinopathy. Proc Natl Acad Sci U S A 96:9176–9180

    Article  Google Scholar 

  12. Deighton RF, McGregor R, Kemp J, McCulloch J, Whittle IR (2010) Glioma pathophysiology: insights emerging from proteomics. Brain Pathol 20:691–701

    Article  PubMed  CAS  Google Scholar 

  13. Le Mercier M, Fortin S, Mathieu V, Kiss R, Lefranc F (2010) Galectins and gliomas. Brain Pathol 20:17–27

    Article  PubMed  Google Scholar 

  14. Miller NL, Wevrick R, Mellon PL (2009) Necdin, a Prader–Willi syndrome candidate gene, regulates gonadotropin-releasing hormone neurons during development. Hum Mol Genet 18:248–260

    Article  PubMed  CAS  Google Scholar 

  15. Kuo MF, Wang HS, Kuo QT, Shun CT, Hsu HC, Yang SH, Yuan RH (2009) High expression of stathmin protein predicts a fulminant course in medulloblastoma. J Neurosurg Pediatr 4:74–80

    Article  PubMed  Google Scholar 

  16. Zanini C, Mandili G, Baci D, Morra I, Forni M (2010) Proteomic profile modification of anaplastic medulloblastoma after in-vivo radiotherapy: a case study. Journal Cancer Therapy 2:97–103. doi:10.4236/jct.2010.12017 http://www.scirp.org/journal/jct

    Google Scholar 

  17. Zhang DY, Ye F, Gao L, Liu X, Zhao X et al (2009) Proteomics, pathway array and signaling network-based medicine in cancer. Cell Div. 4:20

    Google Scholar 

  18. Peyrl A, Krapfenbauer K, Slavc I, Yang JW, Strobel T, Lubec G (2003) Protein profiles of medulloblastoma cell lines DAOY and D283: identification of tumor-related proteins and principles. Proteomics 3:1781–1800

    Article  PubMed  CAS  Google Scholar 

  19. Zanini C, Mandili G, Pulerà F, Morra I, Peretta P, Turrini F, Forni M (2009) Immunohistochemical and proteomic profile of melanotic medulloblastoma. Pediatr Blood Cancer 52:875–877

    Article  PubMed  Google Scholar 

  20. Hoff K, Hartmann W, von Bueren AO, Gerber NU, Grotzer MA, Pietsch T, Rutkowski S (2010) Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors. Pediatr Blood Cancer 54:369–376

    Article  Google Scholar 

  21. Hidvegi T, Ewing M, Hale P, Dippold C, Beckett C, Kemp C, Maurice N, Mukherjee A, Goldbach C, Watkins S, Michalopoulos G, Perlmutter DH (2010) An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science 329:229–232

    Article  PubMed  CAS  Google Scholar 

  22. Mitchell BS (2003) The proteasome—an emerging therapeutic target in cancer. N Engl J Med 348:2597–2598

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The study was partially supported by UGI–Unione Genitori Italiani contro il tumore dei bambini (ugi@ugi-torino.it)–Ospedale Infantile Regina Margherita, Turin, Italy.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Molecular Biotechnology Centre (MBC), University of Turin, Via Nizza 52. CAP, 10126, Torino, Italy

    Cristina Zanini, Denisa Baci & Marco Forni

  2. Research Center for Experimental Medicine (CeRMS), Turin, Italy

    Giorgia Mandili

  3. School of Experimental Pediatrics, University of Turin, Turin, Italy

    Daniele Bertin

  4. Department of Animal Production, Epidemiology and Ecology, MBC, University of Turin, Italy, Turin, Italy

    Francesco Cerutti

  5. Unit of Pediatric Pathology, Ospedale Infantile Regina Margherita, Turin, Italy

    Marco Leone & Isabella Morra

  6. Unit of Pediatrics, University of Turin, Turin, Italy

    Luca di Montezemolo Cordero

Authors
  1. Cristina Zanini
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  2. Giorgia Mandili
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  3. Daniele Bertin
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  4. Francesco Cerutti
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  5. Denisa Baci
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  6. Marco Leone
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  7. Isabella Morra
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  8. Luca di Montezemolo Cordero
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  9. Marco Forni
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Corresponding author

Correspondence to Cristina Zanini.

Electronic supplementary material

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Online Resource 1

Clinical data of patients (DOC 40 kb)

Online Resource 2

Representative colloidal Comassie-stained 2-DE maps of MDB in four different histotypes. Proteins were separated in a pH 3-10NL strips, followed by SDS–PAGE on 10%. After mass spectrometry analysis, 86 unique proteins corresponding to 450 spots cut were identified. Identifications are reported in Tables 1 and 2. Classic MDB (a), desmoplastic/nodular MDB (b), extensive nodularity MDB (c), anaplastic MDB (d) (JPEG 153 kb)

High resolution image file (TIFF 2532 kb)

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Zanini, C., Mandili, G., Bertin, D. et al. Analysis of different medulloblastoma histotypes by two-dimensional gel and MALDI-TOF. Childs Nerv Syst 27, 2077–2085 (2011). https://doi.org/10.1007/s00381-011-1515-9

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  • DOI: https://doi.org/10.1007/s00381-011-1515-9

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