Objective
The genomic landscape of cancer reveals profound complexity, with tumor cells typically accumulating thousands of mutations. While next-generation sequencing maps these alterations across malignancies, translating mutation catalogs into functional and clinically actionable knowledge remains a critical bottleneck in precision oncology. This challenge is exemplified by TP53, a master regulator of cellular stress responses and the most frequently mutated gene in human cancer. Despite its clinical prominence, most TP53 variants remain uncharacterized, with over 1,000 classified as variants of uncertain significance. This reflects the mechanistic and biological complexity of mutant TP53 dysfunction, spanning loss-of-function, gain-of-function, and dominant-negative effects—each shaped by genetic background, cellular identity, and microenvironmental signals. Existing assays fail to capture this multidimensional complexity, limiting actionable insights for clinical decision-making.
TP53in4D will transform TP53 variant interpretation by developing SWAP-IN, an innovative genomic replacement technology enabling saturation mutagenesis of the endogenous TP53 locus under native regulatory control. Applied across diverse cellular models and genetic backgrounds, and integrated with single-cell transcriptomics and time-resolved phenotypic assays, TP53in4D will (1) map variant effects along all functional axes; (2) define how genetic, cellular, and microenvironmental contexts modulate these effects; and (3) build a mechanistic classification framework linking variants to clinical outcome. The resulting resource will resolve long-standing ambiguities in TP53 interpretation, reveal context-specific therapeutic vulnerabilities, and deliver a validated clinical annotation system. Beyond TP53, SWAP-IN establishes a scalable blueprint for decoding cancer genome variation, bridging the gap between mutation detection and biological understanding in precision oncology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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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.
35037 Marburg
Germany
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.