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Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes

Identifieur interne : 003951 ( Main/Exploration ); précédent : 003950; suivant : 003952

Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes

Auteurs : Jose M. C. Tubio [Royaume-Uni] ; Yilong Li [Royaume-Uni] ; Young Seok Ju [Royaume-Uni] ; Inigo Martincorena [Royaume-Uni] ; Susanna L. Cooke [Royaume-Uni] ; Marta Tojo [Espagne] ; Gunes Gundem [Royaume-Uni] ; Christodoulos P. Pipinikas [Royaume-Uni] ; Jorge Zamora [Royaume-Uni] ; Keiran Raine [Royaume-Uni] ; Andrew Menzies [Royaume-Uni] ; Pablo Roman-Garcia [Royaume-Uni] ; Anthony Fullam [Royaume-Uni] ; Moritz Gerstung [Royaume-Uni] ; Adam Shlien [Royaume-Uni] ; Patrick S. Tarpey [Royaume-Uni] ; Elli Papaemmanuil [Royaume-Uni] ; Stian Knappskog [Royaume-Uni, Norvège] ; Peter Van Loo [Royaume-Uni, Belgique] ; Manasa Ramakrishna [Royaume-Uni] ; Helen R. Davies [Royaume-Uni] ; John Marshall [Royaume-Uni] ; David C. Wedge [Royaume-Uni] ; Jon W. Teague [Royaume-Uni] ; Adam P. Butler [Royaume-Uni] ; Serena Nik-Zainal [Royaume-Uni] ; Ludmil Alexandrov [Royaume-Uni] ; Sam Behjati [Royaume-Uni] ; Lucy R. Yates [Royaume-Uni] ; Niccolo Bolli [Royaume-Uni] ; Laura Mudie [Royaume-Uni] ; Claire Hardy [Royaume-Uni] ; Sancha Martin [Royaume-Uni] ; Stuart Mclaren [Royaume-Uni] ; Sarah O'Meara [Royaume-Uni] ; Elizabeth Anderson [Royaume-Uni] ; Mark Maddison [Royaume-Uni] ; Stephen Gamble [Royaume-Uni] ; Christopher Foster [Royaume-Uni] ; Anne Y. Warren [Royaume-Uni] ; Hayley Whitaker [Royaume-Uni] ; Daniel Brewer [Royaume-Uni] ; Rosalind Eeles [Royaume-Uni] ; Colin Cooper [Royaume-Uni] ; David Neal [Royaume-Uni] ; Andy G. Lynch [Royaume-Uni] ; Tapio Visakorpi [Finlande] ; William B. Isaacs [États-Unis] ; Laura Van'T Veer [Pays-Bas] ; Carlos Caldas [Royaume-Uni] ; Christine Desmedt [Belgique] ; Christos Sotiriou [Belgique] ; Sam Aparicio [Canada] ; John A. Foekens [Pays-Bas] ; J Runn Erla Eyfjörd [Islande] ; Sunil R. Lakhani [Australie] ; Gilles Thomas [France] ; Ola Myklebost [Norvège] ; Paul N. Span [Pays-Bas] ; Anne-Lise B Rresen-Dale [Norvège] ; Andrea L. Richardson [États-Unis] ; Marc Van De Vijver [Pays-Bas] ; Anne Vincent-Salomon [France] ; Gert G. Van Den Eynden [Belgique] ; Adrienne M. Flanagan [Royaume-Uni] ; P. Andrew Futreal [Royaume-Uni, États-Unis] ; Sam M. Janes [Royaume-Uni] ; G. Steven Bova [Finlande] ; Michael R. Stratton [Royaume-Uni] ; Ultan Mcdermott [Royaume-Uni] ; Peter J. Campbell [Royaume-Uni]

Source :

RBID : PMC:4380235

Descripteurs français

English descriptors

Abstract

Long interspersed nuclear element–1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3′ transduction. Because 3′ transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3′ transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3′ transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3′ transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.


Url:
DOI: 10.1126/science.1251343
PubMed: 25082706
PubMed Central: 4380235


Affiliations:


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Le document en format XML

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<name sortKey="Behjati, Sam" sort="Behjati, Sam" uniqKey="Behjati S" first="Sam" last="Behjati">Sam Behjati</name>
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<name sortKey="Yates, Lucy R" sort="Yates, Lucy R" uniqKey="Yates L" first="Lucy R." last="Yates">Lucy R. Yates</name>
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<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge</wicri:regionArea>
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<name sortKey="Mudie, Laura" sort="Mudie, Laura" uniqKey="Mudie L" first="Laura" last="Mudie">Laura Mudie</name>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hardy, Claire" sort="Hardy, Claire" uniqKey="Hardy C" first="Claire" last="Hardy">Claire Hardy</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Martin, Sancha" sort="Martin, Sancha" uniqKey="Martin S" first="Sancha" last="Martin">Sancha Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mclaren, Stuart" sort="Mclaren, Stuart" uniqKey="Mclaren S" first="Stuart" last="Mclaren">Stuart Mclaren</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="O Meara, Sarah" sort="O Meara, Sarah" uniqKey="O Meara S" first="Sarah" last="O'Meara">Sarah O'Meara</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Anderson, Elizabeth" sort="Anderson, Elizabeth" uniqKey="Anderson E" first="Elizabeth" last="Anderson">Elizabeth Anderson</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Maddison, Mark" sort="Maddison, Mark" uniqKey="Maddison M" first="Mark" last="Maddison">Mark Maddison</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gamble, Stephen" sort="Gamble, Stephen" uniqKey="Gamble S" first="Stephen" last="Gamble">Stephen Gamble</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Foster, Christopher" sort="Foster, Christopher" uniqKey="Foster C" first="Christopher" last="Foster">Christopher Foster</name>
<affiliation wicri:level="3">
<nlm:aff id="A9">University of Liverpool and HCA Pathology Laboratories, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of Liverpool and HCA Pathology Laboratories, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Warren, Anne Y" sort="Warren, Anne Y" uniqKey="Warren A" first="Anne Y." last="Warren">Anne Y. Warren</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Whitaker, Hayley" sort="Whitaker, Hayley" uniqKey="Whitaker H" first="Hayley" last="Whitaker">Hayley Whitaker</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Brewer, Daniel" sort="Brewer, Daniel" uniqKey="Brewer D" first="Daniel" last="Brewer">Daniel Brewer</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A11">University of East Anglia, Norwich, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of East Anglia, Norwich</wicri:regionArea>
<wicri:noRegion>Norwich</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Cooper, Colin" sort="Cooper, Colin" uniqKey="Cooper C" first="Colin" last="Cooper">Colin Cooper</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A11">University of East Anglia, Norwich, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of East Anglia, Norwich</wicri:regionArea>
<wicri:noRegion>Norwich</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Neal, David" sort="Neal, David" uniqKey="Neal D" first="David" last="Neal">David Neal</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lynch, Andy G" sort="Lynch, Andy G" uniqKey="Lynch A" first="Andy G." last="Lynch">Andy G. Lynch</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Visakorpi, Tapio" sort="Visakorpi, Tapio" uniqKey="Visakorpi T" first="Tapio" last="Visakorpi">Tapio Visakorpi</name>
<affiliation wicri:level="1">
<nlm:aff id="A12">Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Finlande</country>
<wicri:regionArea>Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere</wicri:regionArea>
<wicri:noRegion>Tampere</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Isaacs, William B" sort="Isaacs, William B" uniqKey="Isaacs W" first="William B." last="Isaacs">William B. Isaacs</name>
<affiliation wicri:level="2">
<nlm:aff id="A13">Johns Hopkins University, Baltimore, MD, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Johns Hopkins University, Baltimore, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Veer, Laura Van T" sort="Veer, Laura Van T" uniqKey="Veer L" first="Laura Van'T" last="Veer">Laura Van'T Veer</name>
<affiliation wicri:level="3">
<nlm:aff id="A14">Netherlands Cancer Institute, Amsterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Netherlands Cancer Institute, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Caldas, Carlos" sort="Caldas, Carlos" uniqKey="Caldas C" first="Carlos" last="Caldas">Carlos Caldas</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Desmedt, Christine" sort="Desmedt, Christine" uniqKey="Desmedt C" first="Christine" last="Desmedt">Christine Desmedt</name>
<affiliation wicri:level="4">
<nlm:aff id="A15">Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
<settlement type="city">Bruxelles</settlement>
</placeName>
<orgName type="university">Université libre de Bruxelles</orgName>
</affiliation>
</author>
<author>
<name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name>
<affiliation wicri:level="4">
<nlm:aff id="A15">Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
<settlement type="city">Bruxelles</settlement>
</placeName>
<orgName type="university">Université libre de Bruxelles</orgName>
</affiliation>
</author>
<author>
<name sortKey="Aparicio, Sam" sort="Aparicio, Sam" uniqKey="Aparicio S" first="Sam" last="Aparicio">Sam Aparicio</name>
<affiliation wicri:level="1">
<nlm:aff id="A16">British Columbia Cancer Agency, Vancouver, Canada.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver</wicri:regionArea>
<wicri:noRegion>Vancouver</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Foekens, John A" sort="Foekens, John A" uniqKey="Foekens J" first="John A." last="Foekens">John A. Foekens</name>
<affiliation wicri:level="3">
<nlm:aff id="A17">Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
<placeName>
<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Eyfjord, J Runn Erla" sort="Eyfjord, J Runn Erla" uniqKey="Eyfjord J" first="J Runn Erla" last="Eyfjörd">J Runn Erla Eyfjörd</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Cancer Research Laboratory, University of Iceland, Reykjavik, Iceland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Islande</country>
<wicri:regionArea>Cancer Research Laboratory, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lakhani, Sunil R" sort="Lakhani, Sunil R" uniqKey="Lakhani S" first="Sunil R." last="Lakhani">Sunil R. Lakhani</name>
<affiliation wicri:level="1">
<nlm:aff id="A19">School of Medicine, University of Queensland, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>School of Medicine, University of Queensland, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A20">Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A21">UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>UQ Centre for Clinical Research, University of Queensland, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Thomas, Gilles" sort="Thomas, Gilles" uniqKey="Thomas G" first="Gilles" last="Thomas">Gilles Thomas</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Université Lyon 1, Institut National du Cancer (INCa)–Synergie, Lyon, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Université Lyon 1, Institut National du Cancer (INCa)–Synergie, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Myklebost, Ola" sort="Myklebost, Ola" uniqKey="Myklebost O" first="Ola" last="Myklebost">Ola Myklebost</name>
<affiliation wicri:level="3">
<nlm:aff id="A23">Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Institute for Cancer Research, Oslo University Hospital, Oslo</wicri:regionArea>
<placeName>
<settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Span, Paul N" sort="Span, Paul N" uniqKey="Span P" first="Paul N." last="Span">Paul N. Span</name>
<affiliation wicri:level="3">
<nlm:aff id="A24">Department of Radiation Oncology and Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiation Oncology and Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="B Rresen Dale, Anne Lise" sort="B Rresen Dale, Anne Lise" uniqKey="B Rresen Dale A" first="Anne-Lise" last="B Rresen-Dale">Anne-Lise B Rresen-Dale</name>
<affiliation wicri:level="3">
<nlm:aff id="A23">Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Institute for Cancer Research, Oslo University Hospital, Oslo</wicri:regionArea>
<placeName>
<settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Richardson, Andrea L" sort="Richardson, Andrea L" uniqKey="Richardson A" first="Andrea L." last="Richardson">Andrea L. Richardson</name>
<affiliation wicri:level="2">
<nlm:aff id="A25">Dana-Farber Cancer Institute, Boston, MA, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Dana-Farber Cancer Institute, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Van De Vijver, Marc" sort="Van De Vijver, Marc" uniqKey="Van De Vijver M" first="Marc" last="Van De Vijver">Marc Van De Vijver</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam</wicri:regionArea>
<wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vincent Salomon, Anne" sort="Vincent Salomon, Anne" uniqKey="Vincent Salomon A" first="Anne" last="Vincent-Salomon">Anne Vincent-Salomon</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Institut Bergonié, 229 cours de l’Argone, 33076 Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Institut Bergonié, 229 cours de l’Argone, 33076 Bordeaux</wicri:regionArea>
<wicri:noRegion>33076 Bordeaux</wicri:noRegion>
<wicri:noRegion>33076 Bordeaux</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A28">Institut Curie, Department of Tumor Biology, 26 rue d’Ulm, 75248 Paris cédex 05, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Institut Curie, Department of Tumor Biology, 26 rue d’Ulm, 75248 Paris cédex 05</wicri:regionArea>
<wicri:noRegion>75248 Paris cédex 05</wicri:noRegion>
<wicri:noRegion>75248 Paris cédex 05</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Den Eynden, Gert G" sort="Van Den Eynden, Gert G" uniqKey="Van Den Eynden G" first="Gert G." last="Van Den Eynden">Gert G. Van Den Eynden</name>
<affiliation wicri:level="1">
<nlm:aff id="A29">Translational Cancer Research Unit and Department of Pathology, GZA Hospitals, Antwerp, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Translational Cancer Research Unit and Department of Pathology, GZA Hospitals, Antwerp</wicri:regionArea>
<wicri:noRegion>Antwerp</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Flanagan, Adrienne M" sort="Flanagan, Adrienne M" uniqKey="Flanagan A" first="Adrienne M." last="Flanagan">Adrienne M. Flanagan</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Royal National Orthopaedic Hospital, Middlesex, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Royal National Orthopaedic Hospital, Middlesex</wicri:regionArea>
<wicri:noRegion>Middlesex</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A31">UCL Cancer Institute, University College London, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>UCL Cancer Institute, University College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
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<settlement type="city">Londres</settlement>
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<orgName type="university">University College de Londres</orgName>
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</author>
<author>
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<nlm:aff id="A12">Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Finlande</country>
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</author>
<author>
<name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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<author>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
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<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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<wicri:regionArea>Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
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<affiliation wicri:level="4">
<nlm:aff id="A33">Department of Haematology, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
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<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
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<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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<name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L." last="Cooke">Susanna L. Cooke</name>
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<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
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<nlm:aff id="A2">Department of Physiology, School of Medicine–Center for Resesarch in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Spain.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Espagne</country>
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<region nuts="2" type="region">Galice</region>
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<orgName type="university">Université de Saint-Jacques-de-Compostelle</orgName>
</affiliation>
</author>
<author>
<name sortKey="Gundem, Gunes" sort="Gundem, Gunes" uniqKey="Gundem G" first="Gunes" last="Gundem">Gunes Gundem</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Pipinikas, Christodoulos P" sort="Pipinikas, Christodoulos P" uniqKey="Pipinikas C" first="Christodoulos P." last="Pipinikas">Christodoulos P. Pipinikas</name>
<affiliation wicri:level="4">
<nlm:aff id="A3">Lungs for Living Research Centre, Rayne Institute, University College London (UCL), London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Lungs for Living Research Centre, Rayne Institute, University College London (UCL), London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">University College de Londres</orgName>
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</author>
<author>
<name sortKey="Zamora, Jorge" sort="Zamora, Jorge" uniqKey="Zamora J" first="Jorge" last="Zamora">Jorge Zamora</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Raine, Keiran" sort="Raine, Keiran" uniqKey="Raine K" first="Keiran" last="Raine">Keiran Raine</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Menzies, Andrew" sort="Menzies, Andrew" uniqKey="Menzies A" first="Andrew" last="Menzies">Andrew Menzies</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Roman Garcia, Pablo" sort="Roman Garcia, Pablo" uniqKey="Roman Garcia P" first="Pablo" last="Roman-Garcia">Pablo Roman-Garcia</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fullam, Anthony" sort="Fullam, Anthony" uniqKey="Fullam A" first="Anthony" last="Fullam">Anthony Fullam</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gerstung, Moritz" sort="Gerstung, Moritz" uniqKey="Gerstung M" first="Moritz" last="Gerstung">Moritz Gerstung</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Shlien, Adam" sort="Shlien, Adam" uniqKey="Shlien A" first="Adam" last="Shlien">Adam Shlien</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tarpey, Patrick S" sort="Tarpey, Patrick S" uniqKey="Tarpey P" first="Patrick S." last="Tarpey">Patrick S. Tarpey</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Papaemmanuil, Elli" sort="Papaemmanuil, Elli" uniqKey="Papaemmanuil E" first="Elli" last="Papaemmanuil">Elli Papaemmanuil</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Knappskog, Stian" sort="Knappskog, Stian" uniqKey="Knappskog S" first="Stian" last="Knappskog">Stian Knappskog</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
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<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Department of Clinical Science, University of Bergen, Bergen</wicri:regionArea>
<wicri:noRegion>Bergen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A5">Department of Oncology, Haukeland University Hospital, Bergen, Norway.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Department of Oncology, Haukeland University Hospital, Bergen</wicri:regionArea>
<wicri:noRegion>Bergen</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Loo, Peter" sort="Van Loo, Peter" uniqKey="Van Loo P" first="Peter" last="Van Loo">Peter Van Loo</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A6">Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, Leuven, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Ramakrishna, Manasa" sort="Ramakrishna, Manasa" uniqKey="Ramakrishna M" first="Manasa" last="Ramakrishna">Manasa Ramakrishna</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Davies, Helen R" sort="Davies, Helen R" uniqKey="Davies H" first="Helen R." last="Davies">Helen R. Davies</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Marshall, John" sort="Marshall, John" uniqKey="Marshall J" first="John" last="Marshall">John Marshall</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Wedge, David C" sort="Wedge, David C" uniqKey="Wedge D" first="David C." last="Wedge">David C. Wedge</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Teague, Jon W" sort="Teague, Jon W" uniqKey="Teague J" first="Jon W." last="Teague">Jon W. Teague</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Butler, Adam P" sort="Butler, Adam P" uniqKey="Butler A" first="Adam P." last="Butler">Adam P. Butler</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
</author>
<author>
<name sortKey="Nik Zainal, Serena" sort="Nik Zainal, Serena" uniqKey="Nik Zainal S" first="Serena" last="Nik-Zainal">Serena Nik-Zainal</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Alexandrov, Ludmil" sort="Alexandrov, Ludmil" uniqKey="Alexandrov L" first="Ludmil" last="Alexandrov">Ludmil Alexandrov</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Behjati, Sam" sort="Behjati, Sam" uniqKey="Behjati S" first="Sam" last="Behjati">Sam Behjati</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yates, Lucy R" sort="Yates, Lucy R" uniqKey="Yates L" first="Lucy R." last="Yates">Lucy R. Yates</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Bolli, Niccolo" sort="Bolli, Niccolo" uniqKey="Bolli N" first="Niccolo" last="Bolli">Niccolo Bolli</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A33">Department of Haematology, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mudie, Laura" sort="Mudie, Laura" uniqKey="Mudie L" first="Laura" last="Mudie">Laura Mudie</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Hardy, Claire" sort="Hardy, Claire" uniqKey="Hardy C" first="Claire" last="Hardy">Claire Hardy</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Martin, Sancha" sort="Martin, Sancha" uniqKey="Martin S" first="Sancha" last="Martin">Sancha Martin</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mclaren, Stuart" sort="Mclaren, Stuart" uniqKey="Mclaren S" first="Stuart" last="Mclaren">Stuart Mclaren</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="O Meara, Sarah" sort="O Meara, Sarah" uniqKey="O Meara S" first="Sarah" last="O'Meara">Sarah O'Meara</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Anderson, Elizabeth" sort="Anderson, Elizabeth" uniqKey="Anderson E" first="Elizabeth" last="Anderson">Elizabeth Anderson</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Maddison, Mark" sort="Maddison, Mark" uniqKey="Maddison M" first="Mark" last="Maddison">Mark Maddison</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Gamble, Stephen" sort="Gamble, Stephen" uniqKey="Gamble S" first="Stephen" last="Gamble">Stephen Gamble</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Foster, Christopher" sort="Foster, Christopher" uniqKey="Foster C" first="Christopher" last="Foster">Christopher Foster</name>
<affiliation wicri:level="3">
<nlm:aff id="A9">University of Liverpool and HCA Pathology Laboratories, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of Liverpool and HCA Pathology Laboratories, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Warren, Anne Y" sort="Warren, Anne Y" uniqKey="Warren A" first="Anne Y." last="Warren">Anne Y. Warren</name>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Whitaker, Hayley" sort="Whitaker, Hayley" uniqKey="Whitaker H" first="Hayley" last="Whitaker">Hayley Whitaker</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Brewer, Daniel" sort="Brewer, Daniel" uniqKey="Brewer D" first="Daniel" last="Brewer">Daniel Brewer</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A11">University of East Anglia, Norwich, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of East Anglia, Norwich</wicri:regionArea>
<wicri:noRegion>Norwich</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Eeles, Rosalind" sort="Eeles, Rosalind" uniqKey="Eeles R" first="Rosalind" last="Eeles">Rosalind Eeles</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Cooper, Colin" sort="Cooper, Colin" uniqKey="Cooper C" first="Colin" last="Cooper">Colin Cooper</name>
<affiliation wicri:level="3">
<nlm:aff id="A7">Institute of Cancer Research, Sutton, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Institute of Cancer Research, Sutton, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A11">University of East Anglia, Norwich, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>University of East Anglia, Norwich</wicri:regionArea>
<wicri:noRegion>Norwich</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Neal, David" sort="Neal, David" uniqKey="Neal D" first="David" last="Neal">David Neal</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lynch, Andy G" sort="Lynch, Andy G" uniqKey="Lynch A" first="Andy G." last="Lynch">Andy G. Lynch</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Visakorpi, Tapio" sort="Visakorpi, Tapio" uniqKey="Visakorpi T" first="Tapio" last="Visakorpi">Tapio Visakorpi</name>
<affiliation wicri:level="1">
<nlm:aff id="A12">Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Finlande</country>
<wicri:regionArea>Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere</wicri:regionArea>
<wicri:noRegion>Tampere</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Isaacs, William B" sort="Isaacs, William B" uniqKey="Isaacs W" first="William B." last="Isaacs">William B. Isaacs</name>
<affiliation wicri:level="2">
<nlm:aff id="A13">Johns Hopkins University, Baltimore, MD, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Johns Hopkins University, Baltimore, MD</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Veer, Laura Van T" sort="Veer, Laura Van T" uniqKey="Veer L" first="Laura Van'T" last="Veer">Laura Van'T Veer</name>
<affiliation wicri:level="3">
<nlm:aff id="A14">Netherlands Cancer Institute, Amsterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Netherlands Cancer Institute, Amsterdam</wicri:regionArea>
<placeName>
<settlement type="city">Amsterdam</settlement>
<region nuts="2" type="province">Hollande-Septentrionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Caldas, Carlos" sort="Caldas, Carlos" uniqKey="Caldas C" first="Carlos" last="Caldas">Carlos Caldas</name>
<affiliation wicri:level="4">
<nlm:aff id="A8">Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cancer Research UK (CRUK) Cambridge Institute, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Desmedt, Christine" sort="Desmedt, Christine" uniqKey="Desmedt C" first="Christine" last="Desmedt">Christine Desmedt</name>
<affiliation wicri:level="4">
<nlm:aff id="A15">Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
<settlement type="city">Bruxelles</settlement>
</placeName>
<orgName type="university">Université libre de Bruxelles</orgName>
</affiliation>
</author>
<author>
<name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name>
<affiliation wicri:level="4">
<nlm:aff id="A15">Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels</wicri:regionArea>
<placeName>
<settlement type="city">Bruxelles</settlement>
<region nuts="2">Région de Bruxelles-Capitale</region>
<settlement type="city">Bruxelles</settlement>
</placeName>
<orgName type="university">Université libre de Bruxelles</orgName>
</affiliation>
</author>
<author>
<name sortKey="Aparicio, Sam" sort="Aparicio, Sam" uniqKey="Aparicio S" first="Sam" last="Aparicio">Sam Aparicio</name>
<affiliation wicri:level="1">
<nlm:aff id="A16">British Columbia Cancer Agency, Vancouver, Canada.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Canada</country>
<wicri:regionArea>British Columbia Cancer Agency, Vancouver</wicri:regionArea>
<wicri:noRegion>Vancouver</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Foekens, John A" sort="Foekens, John A" uniqKey="Foekens J" first="John A." last="Foekens">John A. Foekens</name>
<affiliation wicri:level="3">
<nlm:aff id="A17">Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Medical Oncology, Erasmus Medical Center Cancer Institute, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
<placeName>
<settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Eyfjord, J Runn Erla" sort="Eyfjord, J Runn Erla" uniqKey="Eyfjord J" first="J Runn Erla" last="Eyfjörd">J Runn Erla Eyfjörd</name>
<affiliation wicri:level="1">
<nlm:aff id="A18">Cancer Research Laboratory, University of Iceland, Reykjavik, Iceland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Islande</country>
<wicri:regionArea>Cancer Research Laboratory, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lakhani, Sunil R" sort="Lakhani, Sunil R" uniqKey="Lakhani S" first="Sunil R." last="Lakhani">Sunil R. Lakhani</name>
<affiliation wicri:level="1">
<nlm:aff id="A19">School of Medicine, University of Queensland, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>School of Medicine, University of Queensland, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A20">Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A21">UQ Centre for Clinical Research, University of Queensland, Brisbane, Australia.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Australie</country>
<wicri:regionArea>UQ Centre for Clinical Research, University of Queensland, Brisbane</wicri:regionArea>
<wicri:noRegion>Brisbane</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Thomas, Gilles" sort="Thomas, Gilles" uniqKey="Thomas G" first="Gilles" last="Thomas">Gilles Thomas</name>
<affiliation wicri:level="3">
<nlm:aff id="A22">Université Lyon 1, Institut National du Cancer (INCa)–Synergie, Lyon, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Université Lyon 1, Institut National du Cancer (INCa)–Synergie, Lyon</wicri:regionArea>
<placeName>
<region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Myklebost, Ola" sort="Myklebost, Ola" uniqKey="Myklebost O" first="Ola" last="Myklebost">Ola Myklebost</name>
<affiliation wicri:level="3">
<nlm:aff id="A23">Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Institute for Cancer Research, Oslo University Hospital, Oslo</wicri:regionArea>
<placeName>
<settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Span, Paul N" sort="Span, Paul N" uniqKey="Span P" first="Paul N." last="Span">Paul N. Span</name>
<affiliation wicri:level="3">
<nlm:aff id="A24">Department of Radiation Oncology and Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiation Oncology and Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen</wicri:regionArea>
<placeName>
<settlement type="city">Nimègue</settlement>
<region type="province" nuts="2">Gueldre</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="B Rresen Dale, Anne Lise" sort="B Rresen Dale, Anne Lise" uniqKey="B Rresen Dale A" first="Anne-Lise" last="B Rresen-Dale">Anne-Lise B Rresen-Dale</name>
<affiliation wicri:level="3">
<nlm:aff id="A23">Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Norvège</country>
<wicri:regionArea>Institute for Cancer Research, Oslo University Hospital, Oslo</wicri:regionArea>
<placeName>
<settlement type="city">Oslo</settlement>
<region nuts="2">Østlandet</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Richardson, Andrea L" sort="Richardson, Andrea L" uniqKey="Richardson A" first="Andrea L." last="Richardson">Andrea L. Richardson</name>
<affiliation wicri:level="2">
<nlm:aff id="A25">Dana-Farber Cancer Institute, Boston, MA, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>Dana-Farber Cancer Institute, Boston, MA</wicri:regionArea>
<placeName>
<region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Van De Vijver, Marc" sort="Van De Vijver, Marc" uniqKey="Van De Vijver M" first="Marc" last="Van De Vijver">Marc Van De Vijver</name>
<affiliation wicri:level="1">
<nlm:aff id="A26">Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam</wicri:regionArea>
<wicri:noRegion>1105 AZ Amsterdam</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Vincent Salomon, Anne" sort="Vincent Salomon, Anne" uniqKey="Vincent Salomon A" first="Anne" last="Vincent-Salomon">Anne Vincent-Salomon</name>
<affiliation wicri:level="1">
<nlm:aff id="A27">Institut Bergonié, 229 cours de l’Argone, 33076 Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Institut Bergonié, 229 cours de l’Argone, 33076 Bordeaux</wicri:regionArea>
<wicri:noRegion>33076 Bordeaux</wicri:noRegion>
<wicri:noRegion>33076 Bordeaux</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A28">Institut Curie, Department of Tumor Biology, 26 rue d’Ulm, 75248 Paris cédex 05, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>Institut Curie, Department of Tumor Biology, 26 rue d’Ulm, 75248 Paris cédex 05</wicri:regionArea>
<wicri:noRegion>75248 Paris cédex 05</wicri:noRegion>
<wicri:noRegion>75248 Paris cédex 05</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Van Den Eynden, Gert G" sort="Van Den Eynden, Gert G" uniqKey="Van Den Eynden G" first="Gert G." last="Van Den Eynden">Gert G. Van Den Eynden</name>
<affiliation wicri:level="1">
<nlm:aff id="A29">Translational Cancer Research Unit and Department of Pathology, GZA Hospitals, Antwerp, Belgium.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Belgique</country>
<wicri:regionArea>Translational Cancer Research Unit and Department of Pathology, GZA Hospitals, Antwerp</wicri:regionArea>
<wicri:noRegion>Antwerp</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Flanagan, Adrienne M" sort="Flanagan, Adrienne M" uniqKey="Flanagan A" first="Adrienne M." last="Flanagan">Adrienne M. Flanagan</name>
<affiliation wicri:level="1">
<nlm:aff id="A30">Royal National Orthopaedic Hospital, Middlesex, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Royal National Orthopaedic Hospital, Middlesex</wicri:regionArea>
<wicri:noRegion>Middlesex</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A31">UCL Cancer Institute, University College London, London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>UCL Cancer Institute, University College London, London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author>
<name sortKey="Futreal, P Andrew" sort="Futreal, P Andrew" uniqKey="Futreal P" first="P. Andrew" last="Futreal">P. Andrew Futreal</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="A32">MD Anderson Cancer Center, Houston, TX, USA.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea>MD Anderson Cancer Center, Houston, TX</wicri:regionArea>
<placeName>
<region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Janes, Sam M" sort="Janes, Sam M" uniqKey="Janes S" first="Sam M." last="Janes">Sam M. Janes</name>
<affiliation wicri:level="4">
<nlm:aff id="A3">Lungs for Living Research Centre, Rayne Institute, University College London (UCL), London, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Lungs for Living Research Centre, Rayne Institute, University College London (UCL), London</wicri:regionArea>
<placeName>
<settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
<settlement type="city">Londres</settlement>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author>
<name sortKey="Bova, G Steven" sort="Bova, G Steven" uniqKey="Bova G" first="G. Steven" last="Bova">G. Steven Bova</name>
<affiliation wicri:level="1">
<nlm:aff id="A12">Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere, Finland.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Finlande</country>
<wicri:regionArea>Institute of Biosciences and Medical Technology–BioMediTech, University of Tampere and Tampere University Hospital, Tampere</wicri:regionArea>
<wicri:noRegion>Tampere</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Mcdermott, Ultan" sort="Mcdermott, Ultan" uniqKey="Mcdermott U" first="Ultan" last="Mcdermott">Ultan Mcdermott</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name>
<affiliation wicri:level="1">
<nlm:aff id="A1">Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire</wicri:regionArea>
<wicri:noRegion>Cambridgeshire</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="A10">Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge</wicri:regionArea>
<wicri:noRegion>Cambridge</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="A33">Department of Haematology, University of Cambridge, Cambridge, UK.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country>
<wicri:regionArea>Department of Haematology, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName>
<settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Science (New York, N.Y.)</title>
<idno type="ISSN">0036-8075</idno>
<idno type="eISSN">1095-9203</idno>
<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Carcinogenesis (genetics)</term>
<term>Chromatin (chemistry)</term>
<term>DNA Transposable Elements</term>
<term>Exons</term>
<term>Genome, Human</term>
<term>Humans</term>
<term>Long Interspersed Nucleotide Elements</term>
<term>Mutagenesis, Insertional</term>
<term>Neoplasms (genetics)</term>
<term>Transduction, Genetic</term>
<term>Translocation, Genetic</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Carcinogenèse (génétique)</term>
<term>Chromatine ()</term>
<term>Exons</term>
<term>Génome humain</term>
<term>Humains</term>
<term>Mutagenèse par insertion</term>
<term>Transduction génétique</term>
<term>Translocation génétique</term>
<term>Tumeurs (génétique)</term>
<term>Éléments LINE</term>
<term>Éléments transposables d'ADN</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Chromatin</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Carcinogenesis</term>
<term>Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Carcinogenèse</term>
<term>Tumeurs</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>DNA Transposable Elements</term>
<term>Exons</term>
<term>Genome, Human</term>
<term>Humans</term>
<term>Long Interspersed Nucleotide Elements</term>
<term>Mutagenesis, Insertional</term>
<term>Transduction, Genetic</term>
<term>Translocation, Genetic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Chromatine</term>
<term>Exons</term>
<term>Génome humain</term>
<term>Humains</term>
<term>Mutagenèse par insertion</term>
<term>Transduction génétique</term>
<term>Translocation génétique</term>
<term>Éléments LINE</term>
<term>Éléments transposables d'ADN</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="P2">Long interspersed nuclear element–1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3′ transduction. Because 3′ transductions are potentially mutagenic, we explored the extent to which they occur somatically during tumorigenesis. Studying cancer genomes from 244 patients, we found that tumors from 53% of the patients had somatic retrotranspositions, of which 24% were 3′ transductions. Fingerprinting of donor L1s revealed that a handful of source L1 elements in a tumor can spawn from tens to hundreds of 3′ transductions, which can themselves seed further retrotranspositions. The activity of individual L1 elements fluctuated during tumor evolution and correlated with L1 promoter hypomethylation. The 3′ transductions disseminated genes, exons, and regulatory elements to new locations, most often to heterochromatic regions of the genome.</p>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Belgique</li>
<li>Canada</li>
<li>Espagne</li>
<li>Finlande</li>
<li>France</li>
<li>Islande</li>
<li>Norvège</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region>
<li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Auvergne-Rhône-Alpes</li>
<li>Galice</li>
<li>Grand Londres</li>
<li>Gueldre</li>
<li>Hollande-Méridionale</li>
<li>Hollande-Septentrionale</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Rhône-Alpes</li>
<li>Région de Bruxelles-Capitale</li>
<li>Texas</li>
<li>Østlandet</li>
</region>
<settlement>
<li>Amsterdam</li>
<li>Bruxelles</li>
<li>Cambridge</li>
<li>Londres</li>
<li>Lyon</li>
<li>Nimègue</li>
<li>Oslo</li>
<li>Rotterdam</li>
<li>Santiago de Compostela</li>
</settlement>
<orgName>
<li>University College de Londres</li>
<li>Université de Cambridge</li>
<li>Université de Saint-Jacques-de-Compostelle</li>
<li>Université libre de Bruxelles</li>
</orgName>
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<name sortKey="Behjati, Sam" sort="Behjati, Sam" uniqKey="Behjati S" first="Sam" last="Behjati">Sam Behjati</name>
<name sortKey="Bolli, Niccolo" sort="Bolli, Niccolo" uniqKey="Bolli N" first="Niccolo" last="Bolli">Niccolo Bolli</name>
<name sortKey="Bolli, Niccolo" sort="Bolli, Niccolo" uniqKey="Bolli N" first="Niccolo" last="Bolli">Niccolo Bolli</name>
<name sortKey="Brewer, Daniel" sort="Brewer, Daniel" uniqKey="Brewer D" first="Daniel" last="Brewer">Daniel Brewer</name>
<name sortKey="Brewer, Daniel" sort="Brewer, Daniel" uniqKey="Brewer D" first="Daniel" last="Brewer">Daniel Brewer</name>
<name sortKey="Butler, Adam P" sort="Butler, Adam P" uniqKey="Butler A" first="Adam P." last="Butler">Adam P. Butler</name>
<name sortKey="Caldas, Carlos" sort="Caldas, Carlos" uniqKey="Caldas C" first="Carlos" last="Caldas">Carlos Caldas</name>
<name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name>
<name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name>
<name sortKey="Campbell, Peter J" sort="Campbell, Peter J" uniqKey="Campbell P" first="Peter J." last="Campbell">Peter J. Campbell</name>
<name sortKey="Cooke, Susanna L" sort="Cooke, Susanna L" uniqKey="Cooke S" first="Susanna L." last="Cooke">Susanna L. Cooke</name>
<name sortKey="Cooper, Colin" sort="Cooper, Colin" uniqKey="Cooper C" first="Colin" last="Cooper">Colin Cooper</name>
<name sortKey="Cooper, Colin" sort="Cooper, Colin" uniqKey="Cooper C" first="Colin" last="Cooper">Colin Cooper</name>
<name sortKey="Davies, Helen R" sort="Davies, Helen R" uniqKey="Davies H" first="Helen R." last="Davies">Helen R. Davies</name>
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<name sortKey="Nik Zainal, Serena" sort="Nik Zainal, Serena" uniqKey="Nik Zainal S" first="Serena" last="Nik-Zainal">Serena Nik-Zainal</name>
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<name sortKey="Pipinikas, Christodoulos P" sort="Pipinikas, Christodoulos P" uniqKey="Pipinikas C" first="Christodoulos P." last="Pipinikas">Christodoulos P. Pipinikas</name>
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<name sortKey="Tojo, Marta" sort="Tojo, Marta" uniqKey="Tojo M" first="Marta" last="Tojo">Marta Tojo</name>
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<name sortKey="Knappskog, Stian" sort="Knappskog, Stian" uniqKey="Knappskog S" first="Stian" last="Knappskog">Stian Knappskog</name>
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<name sortKey="Knappskog, Stian" sort="Knappskog, Stian" uniqKey="Knappskog S" first="Stian" last="Knappskog">Stian Knappskog</name>
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<name sortKey="Van Loo, Peter" sort="Van Loo, Peter" uniqKey="Van Loo P" first="Peter" last="Van Loo">Peter Van Loo</name>
</noRegion>
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<name sortKey="Van Den Eynden, Gert G" sort="Van Den Eynden, Gert G" uniqKey="Van Den Eynden G" first="Gert G." last="Van Den Eynden">Gert G. Van Den Eynden</name>
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<name sortKey="Bova, G Steven" sort="Bova, G Steven" uniqKey="Bova G" first="G. Steven" last="Bova">G. Steven Bova</name>
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<name sortKey="Isaacs, William B" sort="Isaacs, William B" uniqKey="Isaacs W" first="William B." last="Isaacs">William B. Isaacs</name>
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<name sortKey="Futreal, P Andrew" sort="Futreal, P Andrew" uniqKey="Futreal P" first="P. Andrew" last="Futreal">P. Andrew Futreal</name>
<name sortKey="Richardson, Andrea L" sort="Richardson, Andrea L" uniqKey="Richardson A" first="Andrea L." last="Richardson">Andrea L. Richardson</name>
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<name sortKey="Veer, Laura Van T" sort="Veer, Laura Van T" uniqKey="Veer L" first="Laura Van'T" last="Veer">Laura Van'T Veer</name>
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<name sortKey="Foekens, John A" sort="Foekens, John A" uniqKey="Foekens J" first="John A." last="Foekens">John A. Foekens</name>
<name sortKey="Span, Paul N" sort="Span, Paul N" uniqKey="Span P" first="Paul N." last="Span">Paul N. Span</name>
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<name sortKey="Eyfjord, J Runn Erla" sort="Eyfjord, J Runn Erla" uniqKey="Eyfjord J" first="J Runn Erla" last="Eyfjörd">J Runn Erla Eyfjörd</name>
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<name sortKey="Vincent Salomon, Anne" sort="Vincent Salomon, Anne" uniqKey="Vincent Salomon A" first="Anne" last="Vincent-Salomon">Anne Vincent-Salomon</name>
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