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Pan-cancer functional evaluation of non-coding DNA mutations

Objective

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 251 857,80
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 251 857,80

Partners (1)

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