Objectif The functional evaluation of cancer mutations has been largely restricted to the protein-coding genome, due to our lack of (i) whole-genome sequence data for cancer genomes, and (ii) knowledge about the function of the non-coding genome. However, more recently the function of the non-coding genome has been largely annotated by the ENCODE project, where large consortia are profiling thousands of tumor and matched non-neoplastic tissue samples at the genomic, proteomic and epigenomic levels.Previous studies have shown that (i) over 90% of the disease-associated loci identified with genome-wide association studies (GWAS) lie within the non-coding genome, and (ii) non-coding mutations are frequent in cancer. Nevertheless, few studies have evaluated the role of genetic variation in the non-coding genome in cancer development and progression, and therefore, the landscape of non-coding mutations in cancer remains uncharted territory. Moreover, there are no studies yet relating variation or mutations within the non-coding genome to the sensitivity to drugs, and this is hence the purpose of the work described here.Using genome-wide sequence, epigenomic, transcriptomic, proteomic and eQTL data from (i) over 2,000 whole cancer genomes, (ii) over 10,000 tumor and matched non-neoplastic tissue samples spanning 25 tumor types, and (iii) the ENCODE project, I aim to build a comprehensive map of non-coding mutations across the most prevalent cancer types. Subsequently, this map will be integrated with pharmacological profiles of small molecules in predictive models, thus allowing to identify genetic variants and mutations associated to drug efficacy and resistance across cancers. This work will help unravel the impact of non-coding mutations on genome regulation and gene expression, to disambiguate the contributions of somatic mutations and inherited genetic polymorphisms to cancer susceptibility, and to relate mutations in the non-coding genome to drug efficacy. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Mots‑clés Cancer cancer mutations cancer drivers chemogenomics Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2015-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Appel à propositions H2020-MSCA-IF-2015 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution nette de l'UE € 251 857,80 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Royaume-Uni Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 251 857,80 Partenaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire Partenaire Les organisations partenaires contribuent à la mise en œuvre de l’action, mais ne signent pas la convention de subvention. PRESIDENT AND FELLOWS OF HARVARD COLLEGE États-Unis Contribution nette de l'UE € 0,00 Adresse MASSACHUSETTS AVENUE 1350 02138 Cambridge Voir sur la carte Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 160 130,40