Objectif
Cancer is a complex disease involving multiple genetic and epigenetic events occurring, and influencing each other, over a long period of time. Understanding cancer, and ultimately developing effective targeted therapies, will therefore require that mutations and epigenetic alterations be systematically investigated during the multiple stages of disease development, from identifiable pre-neoplastic phases to overt cancer. Until now, no systematic effort has been undertaken to investigate these multiple layers of genome organization and function during cancer development. MODHEP aims at providing a 360° understanding of liver cancer, one of the most common types of tumors and, because of the homogeneity of the hepatic tissue, the most experimentally tractable one. The consortium brings together elite European scientists in the fields of genetics, chromatin regulation, genomics, liver cancer, computational and systems biology. This combination of skills will allow us to investigate and model at unprecedented resolution the chain of events leading from environmental perturbations and the occurrence of driver mutations to preneoplastic disease and cancer. Our experimental plan reflects some grounded assumptions: 1. cancer cannot be modeled without detailed information on the preneoplastic stages of disease; 2. genetic heterogeneity in humans would make systems-level modeling non realistic from a practical point of view. Both of these limitations are bypassed by the use of well-defined mouse models, followed by evaluation of the main conclusions in clinical samples; 3. many early stage driving events in cancer represent epigenetic alterations, which are invisible to classical genetic analysis, and are confounded by secondary and tertiary events in established tumors. Our approach will enable the identification of therapeutically relevant early-stage genetic and epigenetic alterations and the definition of their interplay in tumor development and maintenance.
Champ scientifique
Appel à propositions
FP7-HEALTH-2010-two-stage
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Régime de financement
CP-IP - Large-scale integrating projectCoordinateur
16163 Genova
Italie
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Participants (17)
75231 Paris
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W1B 1AL LONDON
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1011 JV AMSTERDAM
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00185 Roma
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EH8 9YL Edinburgh
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CB22 3AT Cambridge
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7610001 Rehovot
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351 0198 WAKO SHI SAITAMA
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75724 Paris
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75654 Paris
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69126 Heidelberg
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69002 LYON
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Participation terminée
69002 LYON
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SOUTH BRISBANE
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00179 Roma
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20121 Milano
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WC2R 2LS London
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