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HYPER-INSIGHT SIGNED

Hypermutated tumors: insight into genome maintenance and cancer vulnerabilities provided by an extreme burden of somatic mutations

Total Cost €

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EC-Contrib. €

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Partnership

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 HYPER-INSIGHT project word cloud

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

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Project "HYPER-INSIGHT" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) 

Organization address
address: CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
city: BARCELONA
postcode: 8028
website: www.irbbarcelona.org

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 Spain [ES]
 Total cost 1˙499˙812 €
 EC max contribution 1˙499˙812 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-02-01   to  2023-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA) ES (BARCELONA) coordinator 1˙499˙812.00

Map

 Project objective

Mutations are the fuel of any evolutionary process, and this also applies to carcinogenesis. The advent of affordable DNA sequencing has enabled mutagenic processes in the human soma to be quantified genome-wide, revealing a striking occurrence of hypermutated tumors. They exhibit an extreme load of somatic changes, often harbouring hundreds of single-nucleotide variants and/or indels per megabase. The HYPER-INSIGHT project is organized into three objectives, which aim to take advantage of the unique opportunity provided by genome sequences of hypermutated and ultramutated tumors. In particular, this work planned in this project aims to further our knowledge on (i) the regional organization of the DNA replication and repair program in human cells, and the determinants thereof, (ii) the extent of selection which acts on somatic variants in various pathways or complexes and (iii) opportunities for selectively targeting DNA repair deficiencies that manifest as hypermutation. Methodologically, our work will employ a three-pronged approach. First, we will perform a multitude of rigorous statistical analyses that draw on the rich and still-expanding resources provided by cancer genomics consortia. Second, we will perform exome and genome sequencing, focusing on ultramutated tumors caused by specific defects in the DNA maintenance machinery. Third, the project involves conditional essentiality screens on cancer cell lines with hypermutant backgrounds. Their goal is to discover synthetic lethality relationships, useful for targeting hypermutating cells, while sparing healthy ones. In summary, one of the promises of cancer genome sequencing projects was to elucidate the mechanisms underlying mutational processes in the human soma, advancing our understanding of this important facet of cancer biology. We will work towards realizing this promise, thereby strengthening the EU’s position in the global scientific endeavour.

 Publications

year authors and title journal last update
List of publications.
2019 Fran Supek, Ben Lehner
Scales and mechanisms of somatic mutation rate variation across the human genome
published pages: 102647, ISSN: 1568-7864, DOI: 10.1016/j.dnarep.2019.102647
DNA Repair 81 2019-10-29
2019 Rik Lindeboom, Michiel Vermeulen, Ben Lehner, Fran Supek
The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy
published pages: , ISSN: 1061-4036, DOI: 10.1038/s41588-019-0517-5
Nature Genetics in press 2019-10-29
2019 Marina Salvadores, David Mas-Ponte, Fran Supek
Passenger mutations accurately classify human tumors
published pages: e1006953, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006953
PLOS Computational Biology 15/4 2019-10-29

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