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bECOMiNG SIGNED

spontaneous Evolution and Clonal heterOgeneity in MoNoclonal Gammopathies: from mechanisms of progression to clinical management

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EC-Contrib. €

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Partnership

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 bECOMiNG project word cloud

Explore the words cloud of the bECOMiNG project. It provides you a very rough idea of what is the project "bECOMiNG" about.

identification    specimens    stages    invasive    significantly    screening    lesions    phenotyping    myeloma    trajectory    serial    circulating    correlation    multiple    hematologist    data    gammopathy    biological    replacement    predict    genotyping    scores    clonal    modifier    serve    innovative    vulnerabilities    dissect    prognostic    individuals    healthy    alterations    evolve    free    prospective    precision    bm    preliminary    monoclonal    accurately    determinants    dna    sharp    single    markers    stage    sampling    prediction    list    time    medicine    progression    paradigm    clinical    mms    hypothesis    annotated    samples    mm    disease    candidate    heterogeneity    subpopulations    look    blood    retrospective    cohorts    prevalent    biomarkers    move    outcome    elderly    preceded    mini    detected    collect    onco    analyze    as    expertise    therapies    cancer    last    frequency    hundreds    peripheral    contributed    asymptomatic    archive    genomic    course    phenotypic    follow    evolutionary    hip    marrow    permissive    initiation    conventional    screens    molecularly    rationale    exploited    bone    cells    cell    genotypic    thousands    microenvironment    functionally    aggressive    genomics    evolution    captured   

Project "bECOMiNG" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI MILANO 

Organization address
address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122
website: www.unimi.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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