Obiettivo The successes of cancer research stem from the identification of oncogenes and tumour suppressor genes and the study of their pathways in animal and cell line models. Confronting these models with ‘real life’ human cancer has often been a challenge. This grant aims at integral understanding of the aggressive childhood tumor neuroblastoma. Starting point is a huge database for this tumor. We established mRNA, miRNA, CGH and SNP profiles for a series of neuroblastoma, and sequenced their whole genomes. Over 1500 mRNA profiles of cell lines with manipulated gene expression complete this resource. A novel bioinformatic platform integrated all molecular and clinical data. Several research topics have emerged: (1) Recurrent mutations were detected in neuronal growth cone genes. We will investigate whether failed neuritogenesis is oncogenic; (2) Contrary to the paradigm that cancer is caused by gene mutations, our data suggest that human tumours equally much result from chromosomal gains and losses. They proportionally change the expression of hundreds of otherwise intact genes. We will investigate how copy number changes activate oncogenic pathways. (3) Each neuroblastoma includes two cell types, which at low frequency convert into each other. They differ in mesenchymal and neuro-epithelial character, cancer pathway activation, motility and drug sensitivity and thereby are at the crossroads of cancer stem cell-, drug resistance- and metastasis-research. Transgene expression could induce transitions between both cell types in vitro, which will allow us to elucidate the wiring of both states. (4) Neuroblastoma can go in remission upon treatment, but often relapse as fatal therapy resistant tumour. This plasticity may stem from resistant mesenchymal cells, inter-conversion of cell types and continued chromosomal copy number changes. We will target pathways essential to each cell type to contain plasticity and identify therapeutic options to prepare for clinical testing. Campo scientifico medical and health sciencesclinical medicineallergologydrug allergymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncology Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Invito a presentare proposte ERC-2013-ADG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-AG - ERC Advanced Grant Istituzione ospitante ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Contributo UE € 2 499 802,80 Indirizzo MEIBERGDREEF 15 1105AZ Amsterdam Paesi Bassi Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Hasnae Bouhbouh (Mrs.) Ricercatore principale Rogier Versteeg (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM Paesi Bassi Contributo UE € 2 499 802,80 Indirizzo MEIBERGDREEF 15 1105AZ Amsterdam Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Hasnae Bouhbouh (Mrs.) Ricercatore principale Rogier Versteeg (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato