Project description
Understanding principles of neuroblastoma genome remodelling
Recent studies have revealed that cancer cells have the intrinsic ability to create and re-incorporate extrachromosomal circular DNAs. It has been shown that these genomic events are more frequent in primary human neuroblastomas, a childhood tumour, suggesting that DNA circularisation is a major driver of neuroblastoma genome remodelling. The EU-funded CancerCirculome aims to discover new principles of neuroblastoma genome remodelling, investigating the underlying mechanisms and functional consequences of extrachromosomal DNA circularisation and chromosomal re-integration. The uncovered principles will be applied to identify novel diagnostic and predictive markers for clinical risk assessment and neuroblastoma treatment.
Objective
Recent reports describe the highly unexpected observation that cancer cells have the intrinsic ability to create and chromosomally re-incorporate extrachromosomal circular DNAs. We could show that these genomic phenomena are more frequent than expected in primary human neuroblastomas, a common childhood tumor, suggesting that DNA circularization represents a major driver of neuroblastoma genome remodeling. We aim with CancerCirculome to uncover new principles of pediatric cancer genome remodeling through an intensified study of the underlying mechanisms and functional consequences of extrachromosomal DNA circularization and chromosomal re-integration. Our long-term goal is to exploit these cancer cell-specific traits to improve cancer therapy, diagnosis and/or clinical risk stratification. Our work program will develop and establish new single-cell CRISPR-based methodologies with the aim to reveal molecular factors contributing to circular DNA generation. Furthermore, we will genetically engineer circular DNAs in human cells, assess their functional impact on cancer cell fitness and track their presence and chromosomal integration during therapy on a single-cell level. This aims to uncover the oncogenic functions of circular DNA and reveal the determinants of their chromosomal re-integration. The principles uncovered in CancerCirculome will be dissected to identify novel diagnostic and predictive markers for clinical application to improve personalized diagnosis, risk assessment and treatment of neuroblastoma, as our test case pediatric tumor. The work outlined in CancerCirculome promises to provide key insights into a fundamental biological and clinical problem and stongly impact the understanding of childhood solid tumors. CancerCirculome addresses fundamental questions about how cancer cells could arise and evolve at the roots of clonal evolution in tumors and at the mechanistic level of cellular genetics.
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 DNA
- 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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
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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.
ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2020-STG
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10117 Berlin
Germany
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