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

Project Information

HYPER-INSIGHT

Grant agreement ID: 757700

DOI 10.3030/757700

Project closed

EC signature date 19 September 2017

Start date 1 February 2018

End date 31 January 2024

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost € 1 499 812,50

EU contribution € 1 499 812,50

Coordinated by

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Spain

Publications

Peer reviewed articles (23)

Matching cell lines with cancer type and subtype of origin via mutational, epigenomic, and transcriptomic patterns

Author(s): Marina Salvadores, Francisco Fuster-Tormo, Fran Supek
Published in: Science Advances, Issue 6/27, 2020, Page(s) eaba1862, ISSN 2375-2548
Publisher: American Association for the Advancement of Science
DOI: 10.1126/sciadv.aba1862

Loss of the abasic site sensor HMCES is synthetic lethal with the activity of the APOBEC3A cytosine deaminase in cancer cells

Author(s): Josep Biayna; Isabel Garcia-Cao; Miguel M. Álvarez; Marina Salvadores; Jose Espinosa-Carrasco; Marcel McCullough; Fran Supek; Travis H. Stracker
Published in: PLoS Biology, Issue 15449173, 2022, Page(s) e3001176, ISSN 1544-9173
Publisher: Public Library of Science
DOI: 10.1371/journal.pbio.3001176

The evolutionary signal in metagenome phyletic profiles predicts many gene functions

Author(s): Vedrana Vidulin, Tomislav Šmuc, Sašo Džeroski, Fran Supek
Published in: Microbiome, Issue 6/1, 2018, ISSN 2049-2618
Publisher: BioMed Central
DOI: 10.1186/s40168-018-0506-4

Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type

Author(s): Irene Franco, Hafdis T. Helgadottir, Aldo Moggio, Malin Larsson, Peter Vrtačnik, Anna Johansson, Nina Norgren, Pär Lundin, David Mas-Ponte, Johan Nordström, Torbjörn Lundgren, Peter Stenvinkel, Lars Wennberg, Fran Supek, Maria Eriksson
Published in: Genome Biology, Issue 20/1, 2019, ISSN 1474-760X
Publisher: BioMed Central
DOI: 10.1186/s13059-019-1892-z

The impact of rare germline variants on human somatic mutation processes

Author(s): Mischan Vali-Pour, Ben Lehner, Fran Supek
Published in: Nature Communications, Issue 20411723, 2022, Page(s) 3724, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-31483-1

Cell cycle gene alterations associate with a redistribution of mutation risk across chromosomal domains in human cancers

Author(s): Marina Salvadores, Fran Supek
Published in: Nature Cancer, Issue 5, 2024, Page(s) 330-346, ISSN 2662-1347
Publisher: Springer Nature
DOI: 10.1038/s43018-023-00707-8

Proton and alpha radiation-induced mutational profiles in human cells

Author(s): Tiffany Delhomme, Maia Munteanu, Manuela Buonanno, Veljko Grilj, Josep Biayna, Fran Supek
Published in: Scientific Reports, Issue 13, 2023, Page(s) 9791, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-023-36845-3

DNA mismatch repair promotes APOBEC3-mediated diffuse hypermutation in human cancers

Author(s): David Mas-Ponte, Fran Supek
Published in: Nature Genetics, Issue 52/9, 2020, Page(s) 958-968, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-020-0674-6

Prevalence, causes and impact of TP53-loss phenocopying events in human tumors

Author(s): Bruno Fito-Lopez, Marina Salvadores, Miguel-Martin Alvarez, Fran Supek
Published in: BMC Biology, Issue 21, 2023, Page(s) 92, ISSN 1741-7007
Publisher: BioMed Central
DOI: 10.1186/s12915-023-01595-1

Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation

Author(s): David Mas-Ponte, Fran Supek
Published in: Nucleic Acids Research, 2024, Page(s) gkae252, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkae252

Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy

Author(s): David Mas-Ponte, Marcel McCullough, Fran Supek
Published in: Clinical Science, Issue 01435221, 2022, Page(s) 383–404, ISSN 0143-5221
Publisher: Portland Press, Ltd.
DOI: 10.1042/cs20210682

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

Author(s): Bernardo Rodriguez-Martin, Eva G. Alvarez, Adrian Baez-Ortega, Jorge Zamora, Fran Supek, Jonas Demeulemeester, Martin Santamarina, Young Seok Ju, Javier Temes, Daniel Garcia-Souto, Harald Detering, Yilong Li, Jorge Rodriguez-Castro, Ana Dueso-Barroso, Alicia L. Bruzos, Stefan C. Dentro, Miguel G. Blanco, Gianmarco Contino, Daniel Ardeljan, Marta Tojo, Nicola D. Roberts, Sonia Zumalave, Paul A. W.
Published in: Nature Genetics, Issue 52/3, 2020, Page(s) 306-319, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-019-0562-0

To NMD or Not To NMD: Nonsense-Mediated mRNA Decay in Cancer and Other Genetic Diseases.

Author(s): Fran Supek; Ben Lehner; Ben Lehner; Rik G.H. Lindeboom
Published in: Trends in Genetics, Issue 01689525, 2022, Page(s) 657-668, ISSN 0168-9525
Publisher: Elsevier BV
DOI: 10.1016/j.tig.2020.11.002

Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours

Author(s): Alexandra Avgustinova, Aikaterini Symeonidi, Andrés Castellanos, Uxue Urdiroz-Urricelqui, Llorenç Solé-Boldo, Mercè Martín, Ivan Pérez-Rodríguez, Neus Prats, Ben Lehner, Fran Supek, Salvador Aznar Benitah
Published in: Nature Cell Biology, Issue 20/12, 2018, Page(s) 1400-1409, ISSN 1465-7392
Publisher: Nature Publishing Group
DOI: 10.1038/s41556-018-0233-x

Patterns of diverse gene functions in genomic neighborhoods predict gene function and phenotype

Author(s): Matej Mihelčić, Tomislav Šmuc, Fran Supek
Published in: Scientific Reports, Issue 9/1, 2019, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-019-55984-0

Passenger mutations accurately classify human tumors

Author(s): Marina Salvadores, David Mas-Ponte, Fran Supek
Published in: PLOS Computational Biology, Issue 15/4, 2019, Page(s) e1006953, ISSN 1553-7358
Publisher: Public Library of Science
DOI: 10.1371/journal.pcbi.1006953

Scales and mechanisms of somatic mutation rate variation across the human genome

Author(s): Fran Supek, Ben Lehner
Published in: DNA Repair, Issue 81, 2019, Page(s) 102647, ISSN 1568-7864
Publisher: Elsevier BV
DOI: 10.1016/j.dnarep.2019.102647

The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy

Author(s): Rik Lindeboom, Michiel Vermeulen, Ben Lehner, Fran Supek
Published in: Nature Genetics, Issue in press, 2019, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-019-0517-5

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author(s): Naihui Zhou, Yuxiang Jiang, Timothy R. Bergquist, Alexandra J. Lee, Balint Z. Kacsoh, Alex W. Crocker, Kimberley A. Lewis, George Georghiou, Huy N. Nguyen, Md Nafiz Hamid, Larry Davis, Tunca Dogan, Volkan Atalay, Ahmet S. Rifaioglu, Alperen Dalkıran, Rengul Cetin Atalay, Chengxin Zhang, Rebecca L. Hurto, Peter L. Freddolino, Yang Zhang, Prajwal Bhat, Fran Supek, José M. Fernández, Branislava Ge
Published in: Genome Biology, Issue 20/1, 2019, ISSN 1474-760X
Publisher: BioMed Central
DOI: 10.1186/s13059-019-1835-8

A framework for mutational signature analysis based on DNA shape parameters

Author(s): Aleksandra Karolak; Jurica Levatić; Fran Supek
Published in: PLoS ONE, Issue 19326203, 2022, Page(s) e0262495, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0262495

Mutational signatures are markers of drug sensitivity of cancer cells

Author(s): Jurica Levatic, Marina Salvadores, Francisco Fuster-Tormo, Fran Supek
Published in: Nature Communications, Issue 20411723, 2022, Page(s) 2926, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-30582-3

TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening

Author(s): Miguel Alvarez, Josep Biayna, Fran Supek
Published in: Nature Communications, Issue 20411723, 2022, Page(s) 4520, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-32285-1

Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers.

Author(s): Park, Solip; Supek, Fran; Lehner, Ben; park
Published in: Nature Communications, Issue 20411723, 2021, Page(s) 7051, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-27242-3

Other (3)

Variable efficiency of nonsense-mediated mRNA decay across human tissues, tumors and individuals

Author(s): Guillermo Palou-Marquez, Fran Supek
Published in: bioRxiv, Issue 2024.02.29.582778, 2024, ISSN 2692-8205
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2024.02.29.582778

Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver events of human cancer

Author(s): Elizaveta Besedina, Fran Supek
Published in: bioRxiv, Issue 2023.08.05.552104, 2023, ISSN 2692-8205
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.08.05.552104

Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules

Author(s): Ignasi Toledano, Fran Supek, Ben Lehner
Published in: bioRxiv, Issue 2023.08.07.552350, 2023, ISSN 2692-8205
Publisher: Cold Spring Harbor Laboratory
DOI: 10.1101/2023.08.07.552350