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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
  1. Richard C Turkington1,
  2. Laura A Knight2,
  3. Jaine K Blayney1,
  4. Maria Secrier3,
  5. Rosalie Douglas1,
  6. Eileen E Parkes1,
  7. Eilis K Sutton1,
  8. Leanne Stevenson1,
  9. Damian McManus4,
  10. Sophia Halliday1,
  11. Andrena M McCavigan2,
  12. Gemma E Logan2,
  13. Steven M Walker2,
  14. Christopher J Steele2,
  15. Juliane Perner5,
  16. Jan Bornschein6,
  17. Shona MacRae7,
  18. Ahmad Miremadi8,
  19. Eamon McCarron4,
  20. Stephen McQuaid9,
  21. Kenneth Arthur9,
  22. Jacqueline A James9,
  23. Martin M Eatock1,10,
  24. Robert O’Neill11,
  25. Fergus Noble12,
  26. Timothy J Underwood13,
  27. D Paul Harkin2,
  28. Manuel Salto-Tellez1,
  29. Rebecca C Fitzgerald7,
  30. Richard D Kennedy1,2
  31. on behalf of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group
    1. 1Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
    2. 2Almac Diagnostics Ltd, Craigavon, UK
    3. 3Genetics Institute, University College London, London, UK
    4. 4Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK
    5. 5Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
    6. 6Translational Gastroenterology Unit, John Radcliffe Hospital Oxford University Hospitals NHS Trust, Oxford, UK
    7. 7Hutchison/MRC Research Centre, Cambridge, UK
    8. 8Department of Histopathology, Addenbrookes Hospital, Cambridge, UK
    9. 9Northern Ireland Molecular Pathology Laboratory, Queen’s University Belfast, Belfast, UK
    10. 10Department of Medical Oncology, Belfast Health and Social Care Trust, Belfast, UK
    11. 11Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK
    12. 12Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK
    13. 13Cancer Sciences Division, University of Southampton, Southampton, UK
    1. Correspondence to Dr Richard C Turkington, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, BT9 7BL, UK; r.turkington{at}qub.ac.uk

    Footnotes

    • Contributors RCT, RK and RF contributed to the study concept, design and supervision. RCT had access to all of the data and takes responsibility for data integrity and data analysis. RCT and RK obtained funding for the study. LAK, JKB, MS, AMM, CJS and JP conducted the bioinformatic analysis. All other authors contributed to interpretation of data and critical revision of the manuscript for intellectual content.

    • Funding This work is funded in part by Belfast Health and Social Care Trust Gastrointestinal Cancer Research Fund, Almac Diagnostics, Medical Research Council, Cancer Research UK, HSC Research and Development Division of the Public Health Agency in Northern Ireland, National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and Invest Northern Ireland.

    • Competing interests LAK, AMM, SMW, DPH and RK are employees of Almac Diagnostics and have patent declarations. GEL and CJS are employees of Almac Diagnostics.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators On behalf of the OCCAMS Study Group: Ayesha Noorani (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Paul A W Edwards (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Nicola Grehan (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Barbara Nutzinger (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Caitriona Hughes (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Elwira Fidziukiewicz (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Jason Crawte (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Alex Northrop (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Gianmarco Contino (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Xiaodun Li (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Rachel de la Rue (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Maria O’Donovan (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK) Shalini Malhotra (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK); Monika Tripathi (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK); Simon Tavaré (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Andy G Lynch (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Matthew Eldridge (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Lawrence Bower (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Ginny Devonshire (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Sriganesh Jammula (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Jim Davies (Department of Computer Science, University of Oxford, Oxford, UK); Charles Crichton (Department of Computer Science, University of Oxford, Oxford, UK); Nick Carroll (Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridge, UK); Peter Safranek (Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridge, UK); Andrew Hindmarsh (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK); Vijayendran Sujendran (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK); Stephen J Hayes (Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Medicaland Human Sciences, University of Manchester, Manchester, UK); Yeng Ang (Salford Royal NHS Foundation Trust, Salford, UK; Wigan and Leigh NHS Foundation Trust, Wigan, Manchester, UK; GI Science Centre, University of Manchester, Manchester, UK); Shaun R Preston (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Sarah Oakes (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Izhar Bagwan (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Vicki Save (Edinburgh Royal Infirmary, Edinburgh, UK); Richard J E Skipworth (Edinburgh Royal Infirmary, Edinburgh, UK); Ted R Hupp (Edinburgh Royal Infirmary, Edinburgh, UK); Olga Tucker (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Heart of England NHS Foundation Trust, Birmingham, UK); Andrew Beggs (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK); Philippe Taniere (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK); Sonia Puig (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK); Jack Owsley (University Hospital Southampton NHS Foundation Trust, Southampton, UK); Hugh Barr (Gloucester Royal Hospital, Gloucester, UK); Neil Shepherd (Gloucester Royal Hospital, Gloucester, UK); Oliver Old (Gloucester Royal Hospital, Gloucester, UK); Jesper Lagergren (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; Karolinska Institutet, Stockholm, Sweden) James Gossage (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Andrew Davies (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Fuju Chang (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Janine Zylstra (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Ula Mahadeva (Guy’s and St Thomas’s NHS Foundation Trust, London, UK); Vicky Goh (King’s College London, London, UK); Francesca D Ciccarelli (King’s College London, London, UK); Grant Sanders (Plymouth Hospitals NHS Trust, Plymouth, UK); Richard Berrisford (Plymouth Hospitals NHS Trust, Plymouth, UK); Catherine Harden (Plymouth Hospitals NHS Trust, Plymouth, UK); Mike Lewis (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Ed Cheong (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Bhaskar Kumar (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Simon L Parsons (Nottingham University Hospitals NHS Trust, Nottingham, UK); Irshad Soomro (Nottingham University Hospitals NHS Trust, Nottingham, UK); Philip Kaye (Nottingham University Hospitals NHS Trust, Nottingham, UK); John Saunders (Nottingham University Hospitals NHS Trust, Nottingham, UK); Laurence Lovat (University College London, London, UK); Rehan Haidry (University College London, London, UK); Laszlo Igali (Norfolk and Waveney Cellular Pathology Network, Norwich, UK); Michael Scott (Wythenshawe Hospital, Manchester, UK); Sharmila Sothi (University Hospitals Coventry and Warwickshire NHS, Trust, Coventry, UK); Sari Suortamo (University Hospitals Coventry and Warwickshire NHS, Trust, Coventry, UK); Suzy Lishman (Peterborough Hospitals NHS Trust, Peterborough City Hospital, Peterborough, UK); George B Hanna (Department of Surgery and Cancer, Imperial College London, UK); Krishna Moorthy (Department of Surgery and Cancer, Imperial College London, UK); Christopher J Peters (Department of Surgery and Cancer, Imperial College London, UK); Anna Grabowska (Queen’s Medical Centre, University of Nottingham, Nottingham, UK); and Helen Coleman (Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland, UK).

    • Correction notice This article has been corrected since it published Online First. The author correspondence details have been corrected.

    • Patient consent for publication Not required.

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    Footnotes

    • Contributors RCT, RK and RF contributed to the study concept, design and supervision. RCT had access to all of the data and takes responsibility for data integrity and data analysis. RCT and RK obtained funding for the study. LAK, JKB, MS, AMM, CJS and JP conducted the bioinformatic analysis. All other authors contributed to interpretation of data and critical revision of the manuscript for intellectual content.

    • Funding This work is funded in part by Belfast Health and Social Care Trust Gastrointestinal Cancer Research Fund, Almac Diagnostics, Medical Research Council, Cancer Research UK, HSC Research and Development Division of the Public Health Agency in Northern Ireland, National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and Invest Northern Ireland.

    • Competing interests LAK, AMM, SMW, DPH and RK are employees of Almac Diagnostics and have patent declarations. GEL and CJS are employees of Almac Diagnostics.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators On behalf of the OCCAMS Study Group: Ayesha Noorani (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Paul A W Edwards (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Nicola Grehan (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Barbara Nutzinger (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Caitriona Hughes (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Elwira Fidziukiewicz (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Jason Crawte (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Alex Northrop (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Gianmarco Contino (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Xiaodun Li (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Rachel de la Rue (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK); Maria O’Donovan (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK) Shalini Malhotra (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK); Monika Tripathi (Medical Research Council Cancer Unit, Hutchison/Medical Research Council Research Centre, University of Cambridge, Cambridge, UK, Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK); Simon Tavaré (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Andy G Lynch (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Matthew Eldridge (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Lawrence Bower (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Ginny Devonshire (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Sriganesh Jammula (Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK); Jim Davies (Department of Computer Science, University of Oxford, Oxford, UK); Charles Crichton (Department of Computer Science, University of Oxford, Oxford, UK); Nick Carroll (Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridge, UK); Peter Safranek (Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridge, UK); Andrew Hindmarsh (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK); Vijayendran Sujendran (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK); Stephen J Hayes (Salford Royal NHS Foundation Trust, Salford, UK; Faculty of Medicaland Human Sciences, University of Manchester, Manchester, UK); Yeng Ang (Salford Royal NHS Foundation Trust, Salford, UK; Wigan and Leigh NHS Foundation Trust, Wigan, Manchester, UK; GI Science Centre, University of Manchester, Manchester, UK); Shaun R Preston (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Sarah Oakes (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Izhar Bagwan (Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK); Vicki Save (Edinburgh Royal Infirmary, Edinburgh, UK); Richard J E Skipworth (Edinburgh Royal Infirmary, Edinburgh, UK); Ted R Hupp (Edinburgh Royal Infirmary, Edinburgh, UK); Olga Tucker (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Heart of England NHS Foundation Trust, Birmingham, UK); Andrew Beggs (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK); Philippe Taniere (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK); Sonia Puig (University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK); Jack Owsley (University Hospital Southampton NHS Foundation Trust, Southampton, UK); Hugh Barr (Gloucester Royal Hospital, Gloucester, UK); Neil Shepherd (Gloucester Royal Hospital, Gloucester, UK); Oliver Old (Gloucester Royal Hospital, Gloucester, UK); Jesper Lagergren (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; Karolinska Institutet, Stockholm, Sweden) James Gossage (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Andrew Davies (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Fuju Chang (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Janine Zylstra (Guy’s and St Thomas’s NHS Foundation Trust, London, UK; King’s College London, London, UK); Ula Mahadeva (Guy’s and St Thomas’s NHS Foundation Trust, London, UK); Vicky Goh (King’s College London, London, UK); Francesca D Ciccarelli (King’s College London, London, UK); Grant Sanders (Plymouth Hospitals NHS Trust, Plymouth, UK); Richard Berrisford (Plymouth Hospitals NHS Trust, Plymouth, UK); Catherine Harden (Plymouth Hospitals NHS Trust, Plymouth, UK); Mike Lewis (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Ed Cheong (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Bhaskar Kumar (Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK); Simon L Parsons (Nottingham University Hospitals NHS Trust, Nottingham, UK); Irshad Soomro (Nottingham University Hospitals NHS Trust, Nottingham, UK); Philip Kaye (Nottingham University Hospitals NHS Trust, Nottingham, UK); John Saunders (Nottingham University Hospitals NHS Trust, Nottingham, UK); Laurence Lovat (University College London, London, UK); Rehan Haidry (University College London, London, UK); Laszlo Igali (Norfolk and Waveney Cellular Pathology Network, Norwich, UK); Michael Scott (Wythenshawe Hospital, Manchester, UK); Sharmila Sothi (University Hospitals Coventry and Warwickshire NHS, Trust, Coventry, UK); Sari Suortamo (University Hospitals Coventry and Warwickshire NHS, Trust, Coventry, UK); Suzy Lishman (Peterborough Hospitals NHS Trust, Peterborough City Hospital, Peterborough, UK); George B Hanna (Department of Surgery and Cancer, Imperial College London, UK); Krishna Moorthy (Department of Surgery and Cancer, Imperial College London, UK); Christopher J Peters (Department of Surgery and Cancer, Imperial College London, UK); Anna Grabowska (Queen’s Medical Centre, University of Nottingham, Nottingham, UK); and Helen Coleman (Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Northern Ireland, UK).

    • Correction notice This article has been corrected since it published Online First. The author correspondence details have been corrected.

    • Patient consent for publication Not required.

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