Proteomic studies of pediatric medulloblastoma tumors with 17p deletion.

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.

Proteomics studies of childhood pilocytic astrocytoma.

Childhood pilocytic astrocytoma is the most frequent brain tumor affecting children. Proteomics analysis is currently considered a powerful tool for global evaluation of protein expression and has been widely applied in the field of cancer research. In the present study, a series of proteomics, genomics, and bioinformatics approaches were employed to identify, classify and characterize the proteome content of low-grade brain tumors as it appears in early childhood. Through bioinformatics database construction, protein profiles generated from pathological tissue samples were compared against profiles of normal brain tissues. Additionally, experiments of comparative genomic hybridization arrays were employed to monitor for genetic aberrations and sustain the interpretation and evaluation of the proteomic data. The current study confirms the dominance of MAPK pathway for the childhood pilocytic astrocytoma occurrence and novel findings regarding the ERK-2 expression are reported.

The frequency of NPM1 mutations in childhood acute myeloid leukemia.

BACKGROUND: Mutations in the nucleophosmin (NPM1) gene have been solely associated with childhood acute myeloid leukemia (AML). We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations. RESULTS: NPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290) and (S293) in the NPM protein. FLT3/ITD mutations were observed in 12% of the cases and in one NPM1-mutated case bearing also t(8;21) (q22;q22). No common RAS mutations were identified. CONCLUSIONS: A relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.