title: Integrated proteomic platforms for the comparative characterization of medulloblastoma and pilocytic astrocytoma pediatric brain tumors: a preliminary study.
abstract: A top-down/bottom-up integrated proteomic approach based on LC-MS and 2-DE analysis was applied for comparative characterization of medulloblastoma and pilocytic astrocytoma posterior cranial fossa pediatric brain tumor tissues. Although rare, primary brain tumors are the most frequent solid tumors in the pediatric age. Among them the medulloblastoma is the prevalent malignant tumor in childhood while pilocytic astrocytoma is the most common, rarely showing a malignant progression. Due to the limited availability of this kind of sample, the study was applied to pooled tumor tissues for a preliminary investigation. The results showed different proteomic profiles of the two tumors and evidenced interesting differential expression of several proteins and peptides. Top-down proteomics of acid-soluble fractions of brain tumor homogenates ascribed a potential biomarker role of malignancy to β- and α-thymosins and their truncated proteoforms and to C-terminal truncated (des-GG) ubiquitin, resulting exclusively detected or over-expressed in the highly malignant medulloblastoma. The bottom-up proteomics of the acid-soluble fraction identified several proteins, some of them in common with 2-DE analysis of acid-insoluble pellets. Peroxiredoxin-1, peptidyl-prolyl cis-trans isomerase A, triosephosphate isomerase, pyruvate kinase PKM, tubulin beta and alpha chains, heat shock protein HSP-90-beta and different histones characterized the medulloblastoma while the Ig kappa chain C region, serotransferrin, tubulin beta 2A chain and vimentin the pilocytic astrocytoma. The two proteomic strategies, with their pros and cons, well complemented each other in characterizing the proteome of brain tumor tissues and in disclosing potential disease biomarkers to be validated in a future study on individual samples of both tumor histotypes.
authors.affiliation: Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martelli
authors.forename: Federica
authors.initials: F
authors.lastname: Iavarone
authors.forename: Luca
authors.initials: L
authors.lastname: D'Angelo
authors.forename: Morena
authors.initials: M
authors.lastname: Arba
authors.forename: Federica
authors.initials: F
authors.lastname: Vincenzoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Inserra
authors.forename: Daniela
authors.initials: D
authors.lastname: Delfino
authors.forename: Diana Valeria
authors.initials: DV
authors.lastname: Rossetti
authors.forename: Marta
authors.initials: M
authors.lastname: Caretto
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Tamburrini
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
authors.forename: Massimo
authors.initials: M
authors.lastname: Caldarelli
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sanna
authors.forename: Claudia
authors.initials: C
authors.lastname: Desiderio
mesh_terms: D001254:Astrocytoma / Q000737:chemistry* / Q000378:metabolism; D001932:Brain Neoplasms / Q000737:chemistry* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008527:Medulloblastoma / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics
chemical_list: D011506:Proteins; D020543:Proteome