The evolution of non-small cell lung cancer metastases in TRACERx

Accepted/In Press date: 12 January 2023

e-pub ahead of print date: 12 April 2023

Published date: 20 April 2023

Additional Information: Funding Information: The TRACERx study (ClinicalTrials.gov: NCT01888601) is sponsored by University College London (UCL/12/0279) and has been approved by an independent Research Ethics Committee (13/LO/1546). TRACERx is funded by Cancer Research UK (C11496/A17786) and is coordinated through the Cancer Research UK and UCL Cancer Trials Centre, which has a core grant from CRUK (C444/A15953). We thank the patients and relatives who participated in the TRACERx study; all site personnel, investigators, funders and industry partners who supported the generation of the data within this study; the staff at the Scientific Computing, the Advanced Sequencing Facility and Experimental Histopathology departments at the Francis Crick Institute for their support; and J. Brock from Research Illustration for his help. This work was supported by the Cancer Research UK Lung Cancer Centre of Excellence, the CRUK City of London Centre Award (C7893/A26233) and the UCL Experimental Cancer Medicine Centre. M.A.B. is supported by Cancer Research UK, the Rosetrees Trust and the Francis Crick Institute; A.Hu. by Cancer Research UK; C.M.-R. by the Rosetrees (M630) and Wellcome trusts; T.B.K.W. by the Francis Crick Institute, as well as the Marie Curie ITN Project PLOIDYNET (FP7-PEOPLE-2013, 607722), Breast Cancer Research Foundation (BCRF), Royal Society Research Professorships Enhancement Award (RP/EA/180007) and the Foulkes Foundation; D.A.M. by the Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025); A.R. by the Francis Crick Institute; S.H. by Cancer Research UK and the Rosetrees Trust; M.D. by Cancer Research UK and the Lung Cancer Centre of Excellence; E.C. by Cancer Research UK (TRACERx (C11496/A17786)) and the Francis Crick Institute; A.M.F. by Stand Up To Cancer (SU2C-AACR-DT23-17); E.L.L. by NovoNordisk Foundation (ID 16584); T.K. by the JSPS Overseas Research Fellowships Program (202060447); C.T.H. by the NIHR University College London Hospitals Biomedical Research Centre; F.H.B. by the Manchester NIHR CRF; A.N. by Cancer Research UK and the Department of Health’s NIHR Biomedical Research Centre’s funding scheme; N.N. by a Medical Research Council Clinical Academic Research Partnership (MR/T02481X/1). S.M.J. is supported by CRUK programme grant (EDDCPGM\100002), and MRC Programme grant (MR/W025051/1), and receives support from the CRUK Lung Cancer Centre and the CRUK City of London Centre, the Rosetrees Trust, the Roy Castle Lung Cancer foundation, the Longfonds BREATH Consortia, MRC UKRMP2 Consortia, the Garfield Weston Trust and University College London Hospitals Charitable Foundation and his work was partly undertaken at UCLH/UCL, which receives some funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme. M.D.F. is supported by the UCL/UCLH NIHR Biomedical Research Centre and runs early-phase studies in the NIHR UCLH Clinical Research Facility supported by the UCL ECMC. S.M.L is partially supported by UCL/UCLH NIHR Biomedical Centre. S.A.Q. is funded by a Cancer Research UK (CRUK) Senior Cancer Research Fellowship (C36463/A22246) and a CRUK Biotherapeutic Program grant (C36463/A20764). P.V.L. was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2008), the UK Medical Research Council (CC2008) and the Wellcome Trust (CC2008); is a Winton Group Leader in recognition of the Winton Charitable Foundation’s support towards the establishment of The Francis Crick Institute; and is a CPRIT Scholar in Cancer Research and acknowledges CPRIT grant support (RR210006). C.D. acknowledges funding received from Cancer Research UK through the CRUK Manchester Institute (A27412), the CRUK Manchester Centre (CTRQQR-2021\100010) and CRUK Lung Cancer Centre of Excellence (A29240) and is supported by the NIHR Manchester Biomedical Research Centre. N.B.J. is a fellow of the Lundbeck Foundation (R272-2017-4040) and acknowledges funding from Aarhus University Research Foundation (AUFF-E-2018-7-14) and the Novo Nordisk Foundation (NNF21OC0071483).S.Z. is a Cancer Research UK Career Development Fellow (RCCCDF-Nov21\100005) and is also supported by Rosetrees Trust (M917). S.Z. and A.B. are also supported by a Cancer Research UK UCL Centre Non-Clinical Training Award (CANTAC721\100022). M.J.-H. is a CRUK Career Establishment Awardee and has received funding from CRUK, IASLC International Lung Cancer Foundation, Lung Cancer Research Foundation, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Centre. N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (211179/Z/18/Z) and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals and the CRUK University College London Experimental Cancer Medicine Centre. C.S. is a Royal Society Napier Research Professor (RSRP\R\210001); is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (CC2041), the UK Medical Research Council (CC2041) and the Wellcome Trust (CC2041). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. C.S. is funded by Cancer Research UK (TRACERx (C11496/A17786), PEACE (C416/A21999) and CRUK Cancer Immunotherapy Catalyst Network); Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025); the Rosetrees Trust, Butterfield and Stoneygate Trusts; NovoNordisk Foundation (ID16584); Royal Society Professorship Enhancement Award (RP/EA/180007); National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre; the Cancer Research UK–University College London Centre; the Experimental Cancer Medicine Centre; the Breast Cancer Research Foundation (US); the Mark Foundation for Cancer Research Aspire Award (21-029-ASP); and is in receipt of an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (835297). This work was supported by a Stand Up To Cancer‐LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17 to S. M. Dubinett and A. E. Spira). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. Funding Information: The TRACERx study (ClinicalTrials.gov: NCT01888601) is sponsored by University College London (UCL/12/0279) and has been approved by an independent Research Ethics Committee (13/LO/1546). TRACERx is funded by Cancer Research UK (C11496/A17786) and is coordinated through the Cancer Research UK and UCL Cancer Trials Centre, which has a core grant from CRUK (C444/A15953). We thank the patients and relatives who participated in the TRACERx study; all site personnel, investigators, funders and industry partners who supported the generation of the data within this study; the staff at the Scientific Computing, the Advanced Sequencing Facility and Experimental Histopathology departments at the Francis Crick Institute for their support; and J. Brock from Research Illustration for his help. This work was supported by the Cancer Research UK Lung Cancer Centre of Excellence, the CRUK City of London Centre Award (C7893/A26233) and the UCL Experimental Cancer Medicine Centre. M.A.B. is supported by Cancer Research UK, the Rosetrees Trust and the Francis Crick Institute; A.Hu. by Cancer Research UK; C.M.-R. by the Rosetrees (M630) and Wellcome trusts; T.B.K.W. by the Francis Crick Institute, as well as the Marie Curie ITN Project PLOIDYNET (FP7-PEOPLE-2013, 607722), Breast Cancer Research Foundation (BCRF), Royal Society Research Professorships Enhancement Award (RP/EA/180007) and the Foulkes Foundation; D.A.M. by the Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025); A.R. by the Francis Crick Institute; S.H. by Cancer Research UK and the Rosetrees Trust; M.D. by Cancer Research UK and the Lung Cancer Centre of Excellence; E.C. by Cancer Research UK (TRACERx (C11496/A17786)) and the Francis Crick Institute; A.M.F. by Stand Up To Cancer (SU2C-AACR-DT23-17); E.L.L. by NovoNordisk Foundation (ID 16584); T.K. by the JSPS Overseas Research Fellowships Program (202060447); C.T.H. by the NIHR University College London Hospitals Biomedical Research Centre; F.H.B. by the Manchester NIHR CRF; A.N. by Cancer Research UK and the Department of Health’s NIHR Biomedical Research Centre’s funding scheme; N.N. by a Medical Research Council Clinical Academic Research Partnership (MR/T02481X/1). S.M.J. is supported by CRUK programme grant (EDDCPGM\100002), and MRC Programme grant (MR/W025051/1), and receives support from the CRUK Lung Cancer Centre and the CRUK City of London Centre, the Rosetrees Trust, the Roy Castle Lung Cancer foundation, the Longfonds BREATH Consortia, MRC UKRMP2 Consortia, the Garfield Weston Trust and University College London Hospitals Charitable Foundation and his work was partly undertaken at UCLH/UCL, which receives some funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme. M.D.F. is supported by the UCL/UCLH NIHR Biomedical Research Centre and runs early-phase studies in the NIHR UCLH Clinical Research Facility supported by the UCL ECMC. S.M.L is partially supported by UCL/UCLH NIHR Biomedical Centre. S.A.Q. is funded by a Cancer Research UK (CRUK) Senior Cancer Research Fellowship (C36463/A22246) and a CRUK Biotherapeutic Program grant (C36463/A20764). P.V.L. was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2008), the UK Medical Research Council (CC2008) and the Wellcome Trust (CC2008); is a Winton Group Leader in recognition of the Winton Charitable Foundation’s support towards the establishment of The Francis Crick Institute; and is a CPRIT Scholar in Cancer Research and acknowledges CPRIT grant support (RR210006). C.D. acknowledges funding received from Cancer Research UK through the CRUK Manchester Institute (A27412), the CRUK Manchester Centre (CTRQQR-2021\100010) and CRUK Lung Cancer Centre of Excellence (A29240) and is supported by the NIHR Manchester Biomedical Research Centre. N.B.J. is a fellow of the Lundbeck Foundation (R272-2017-4040) and acknowledges funding from Aarhus University Research Foundation (AUFF-E-2018-7-14) and the Novo Nordisk Foundation (NNF21OC0071483).S.Z. is a Cancer Research UK Career Development Fellow (RCCCDF-Nov21\100005) and is also supported by Rosetrees Trust (M917). S.Z. and A.B. are also supported by a Cancer Research UK UCL Centre Non-Clinical Training Award (CANTAC721\100022). M.J.-H. is a CRUK Career Establishment Awardee and has received funding from CRUK, IASLC International Lung Cancer Foundation, Lung Cancer Research Foundation, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Centre. N.M. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (211179/Z/18/Z) and also receives funding from Cancer Research UK, Rosetrees and the NIHR BRC at University College London Hospitals and the CRUK University College London Experimental Cancer Medicine Centre. C.S. is a Royal Society Napier Research Professor (RSRP\R\210001); is supported by the Francis Crick Institute that receives its core funding from Cancer Research UK (CC2041), the UK Medical Research Council (CC2041) and the Wellcome Trust (CC2041). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. C.S. is funded by Cancer Research UK (TRACERx (C11496/A17786), PEACE (C416/A21999) and CRUK Cancer Immunotherapy Catalyst Network); Cancer Research UK Lung Cancer Centre of Excellence (C11496/A30025); the Rosetrees Trust, Butterfield and Stoneygate Trusts; NovoNordisk Foundation (ID16584); Royal Society Professorship Enhancement Award (RP/EA/180007); National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre; the Cancer Research UK–University College London Centre; the Experimental Cancer Medicine Centre; the Breast Cancer Research Foundation (US); the Mark Foundation for Cancer Research Aspire Award (21-029-ASP); and is in receipt of an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (835297). This work was supported by a Stand Up To Cancer‐LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17 to S. M. Dubinett and A. E. Spira). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. Publisher Copyright: © 2023, The Author(s).

Keywords: carcinoma, non-small-cell lung/pathology, clonal evolution, clone cells/pathology, cohort studies, disease progression, evolution, molecular, humans, lung neoplasms/pathology, neoplasm metastasis/diagnosis, neoplasm recurrence, local

Local EPrints ID: 477650

URI: http://eprints.soton.ac.uk/id/eprint/477650

DOI: doi:10.1038/s41586-023-05729-x

ISSN: 0028-0836

PURE UUID: 52af41d0-c134-4b11-b1a8-8724d28b074f

Date deposited: 12 Jun 2023 16:41

Last modified: 17 Mar 2024 02:03