Proteomic integrated platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors

C. Martelli;SANNA, MARIA TERESA;ARBA, MORENA;I. Messana;F. Iavarone;M. Castagnola;L. D'Angelo;M. Caretto;G. Tamburrini;C. Di Rocco;M. Caldarelli;C. Desiderio

2014-01-01

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Abstract

Brain tumors represent the most frequent solid tumors occurring in pediatric age. Although their morphological and molecular heterogeneity has been widely investigated, the mechanisms involved in the oncogenesis of brain tumors are partly still unknown. Surgery remains the main treatment and serious damages can often occur due to the tricky tumor localization. Among pediatric brain tumor diseases, posterior cranial fossa tumors are the most frequent including medulloblastoma (malignant lesion, WHO grade IV) and pilocytic astrocytoma (benign lesion, WHO grade I). Few proteomics studies were devoted to the characterization of the protein component of these neoplasms [1-4], and none of them utilizing top-down platforms. In this study we focused on the comparative proteomic analysis of medulloblastoma and pilocytic astrocytoma tumor tissues collected during surgery. An integrated top-down/bottom-up proteomic platform was applied and all the samples were processed by means of LC-ESI-LTQ-Orbitrap apparatus. The top-down preoteomic analysis evidenced in the most aggressive medulloblastoma tumor specific proteoforms of ubiquitin, β-thymosins, α-thymosins, which could be therefore biomarkers of malignancy. 2D-gel electrophoresis analysis evidenced a number of spots differentially expressed in the two samples: GFAP protein, an immunocytological marker for pilocytic astrocytoma, as well as serotransferrin are present as two trains of charged spots in pilocytic astrocytoma only (5.1 and 5.2 fold increase, respectively), while peroxiredoxin-1, nucleoside diphosphate kinase A and B (Nm 23-H1 and Nm23-H2) are 6.4, 3.0 and 2.0 fold overexpressed in medulloblastoma, respectively.