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HEpatocellular carcinoma GErmline MutatiONs ImpaCt (HEGEMONIC)

Objective

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. Although several environmental factors have been identified, many affected individuals never develop HCC, suggesting a genetic susceptibility. Candidate genes and genome-wide association studies (GWAS) have only uncovered a few variants reproducibly linked to HCC. GWAS design typically allows the detection of common variants that usually have small effect sizes. Even taken together, they explain a very limited proportion of the heritability. This could reflect the presence of rare variants that may confer very large effect sizes. These may be captured by next-generation sequencing (NGS). Whole exome sequencing (WES) of thousands of tumors has defined the somatic genetic landscape of the most common cancers. Using WES, the host group has strongly contributed to the identification of the major pathways recurrently mutated in HCC. Nevertheless, despite the large amount of NGS data generated by cancer genome projects, the analysis of rare germline variants (i.e. variation pre-existing in normal cells) is currently a neglected field, particularly in liver carcinogenesis. The HEGEMONIC project hypothesizes that rare variants in coding regions of the genome (exome) impact the risk of HCC. This project proposes an integrative approach combining (epi)genomic information generated by the host group and from publicly available sources. First, the applicant will compare WES data from a series of 350 patients with HCC to nearly 70,000 controls compiled by the Exome Aggregation and UK10K consortia. Then, validation of the top signals will be performed by conventional sequencing in three replication cohorts. Finally, the applicant will analyze genotype-phenotype associations, taking advantage of the extensive clinical data available. Ultimately, the HEGEMONIC project may generate new biological hypotheses in liver carcinogenesis and identify new biomarkers and pharmaceutical targets.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2016

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Coordinator

UNIVERSITE PARIS CITE
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.

€ 173 076,00
Address
85 BD SAINT GERMAIN
75006 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
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.

€ 173 076,00
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