bECOMiNG SIGNED
spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management
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Project "bECOMiNG" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITA DEGLI STUDI DI MILANO
Organization address contact info |
| Coordinator Country | Italy [IT] |
| Total cost | 1˙998˙781 € |
| EC max contribution | 1˙998˙781 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2018-COG |
| Funding Scheme | ERC-COG |
| Starting year | 2019 |
| Duration (year-month-day) | from 2019-03-01 to 2024-02-29 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITA DEGLI STUDI DI MILANO | IT (MILANO) | coordinator | 1˙998˙781.00 |
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Project objective
As an onco-hematologist with a strong expertise in genomics, I significantly contributed to the understanding of multiple myeloma (MM) heterogeneity and its evolution over time, driven by genotypic and phenotypic features carried by different subpopulations of cells. MM is preceded by prevalent, asymptomatic stages that may evolve with variable frequency, not accurately captured by current clinical prognostic scores. Supported by preliminary data, my hypothesis is that the same heterogeneity is present early on the disease course, and identification of the biological determinants of evolution at this stage will allow better prediction of its evolutionary trajectory, if not its control. In this proposal I will therefore make a sharp change from conventional approaches and move to early stages of MM using unique retrospective sample cohorts and ambitious prospective sampling. To identify clonal MM cells in the elderly before a monoclonal gammopathy can be detected, I will collect bone marrow (BM) from hundreds of hip replacement specimens, and analyze archive peripheral blood samples of thousands of healthy individuals with years of annotated clinical follow-up. This will identify early genomic alterations that are permissive to disease initiation/evolution and may serve as biomarkers for clinical screening. Through innovative, integrated single-cell genotyping and phenotyping of hundreds of asymptomatic MMs, I will functionally dissect heterogeneity and characterize the BM microenvironment to look for determinants of disease progression. Correlation with clinical outcome and mini-invasive serial sampling of circulating cell-free DNA will identify candidate biological markers to better predict evolution. Last, aggressive modelling of candidate early lesions and modifier screens will offer a list of vulnerabilities that could be exploited for rationale therapies. These methodologies will deliver a paradigm for the use of molecularly-driven precision medicine in cancer.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Maura, Francesco; Degasperi, Andrea; Nadeu, Ferran; Leongamornlert, Daniel; Davies, Helen; Moore, Luiza; Royo, Romina; Ziccheddu, Bachisio; Puente, Xose S.; Avet-Loiseau, Herve; Cambell, Peter J.; Nik-Zainal, Nik; Campo, Elias; Munshi, Nikhil; Bolli, Niccolò A practical guide for mutational signature analysis in hematological malignancies published pages: , ISSN: 2041-1723, DOI: 10.17863/CAM.41719 |
Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) 1 | 2020-03-05 |
| 2019 |
Francesco Maura, Niccoló Bolli, Nicos Angelopoulos, Kevin J. Dawson, Daniel Leongamornlert, Inigo Martincorena, Thomas J. Mitchell, Anthony Fullam, Santiago Gonzalez, Raphael Szalat, Federico Abascal, Bernardo Rodriguez-Martin, Mehmet Kemal Samur, Dominik Glodzik, Marco Roncador, Mariateresa Fulciniti, Yu Tzu Tai, Stephane Minvielle, Florence Magrangeas, Philippe Moreau, Paolo Corradini, Kenneth Genomic landscape and chronological reconstruction of driver events in multiple myeloma published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-11680-1 |
Nature Communications 10/1 | 2020-03-05 |
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