title: Proteomic studies of pediatric medulloblastoma tumors with 17p deletion.
abstract: CNS tumors are the leading cause of cancer-related death in children. Medulloblastoma is the commonest pediatric CNS malignancy, wherein, despite multimodal therapy with surgery, radiation, and chemotherapy, 5 year survival rates merely approach 60%. Until present, gene expression and cytogenetic studies have produced contradicting findings regarding the molecular background of the specific disease. Through integration of genomics, bioinformatics, and proteomics, the current study aims to shed light at the proteomic-related molecular events responsible for MBL pathophysiology, as well as to provide molecular/protein/pathway answers concerning tumor-onset. Experiments were performed on tissues collected at surgery. With 17p loss being the commonest chromosomal aberrance observed in our sample set, array-CGH were employed to first distinguish for 17p-positive cases. 2-DE coupled to mass spectrometry identification exposed the MBL-specific protein profile. Protein profiles of malignant tissues were compared against profiles of normal cerebellar tissues, and quantitative protein differences were determined. Bioinformatics, functional and database analyses, characterization, and subnetwork profiling generated information on MBL protein interactions. Key molecules of the PI3K/mTOR signaling network were identified via the techniques applied herein. Among the findings IGF2, PI3K, Rictor, MAPKAP1, S6K1, 4EBP1, and ELF4A, as part of the IGF network (implicating PI3K/mTOR), were founded to be deregulated.
authors.affiliation: Proteomics Research Unit, Center of Basic Research II, Biomedical Research Foundation of the Academy of Athens , Athens 115 27, Greece.
authors.forename: Athanasios K
authors.initials: AK
authors.lastname: Anagnostopoulos
authors.forename: Chrissa
authors.initials: C
authors.lastname: Papathanassiou
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Karamolegou
authors.forename: Ema
authors.initials: E
authors.lastname: Anastasiadou
authors.forename: Konstantinos S
authors.initials: KS
authors.lastname: Dimas
authors.forename: Harry
authors.initials: H
authors.lastname: Kontos
authors.forename: Anastasios
authors.initials: A
authors.lastname: Koutsopoulos
authors.forename: Neofytos
authors.initials: N
authors.lastname: Prodromou
authors.forename: Fotini
authors.initials: F
authors.lastname: Tzortzatou-Stathopoulou
authors.forename: George Th
authors.initials: GT
authors.lastname: Tsangaris
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics
keywords: 17p deletion; medulloblastoma; pediatric brain tumors; proteomics; surgical specimen