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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.

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

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

Map

 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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