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.