A mechanistic classification of clinical phenotypes in neuroblastoma

Sandra Ackermann; Maria Cartolano; Barbara Hero; Anne Welte; Yvonne Kahlert; Andrea Roderwieser; Christoph Bartenhagen; Esther Walter; Judith Gecht; Laura Kerschke; Ruth Volland; Roopika Menon; Johannes M. Heuckmann; Moritz Gartlgruber; Sabine Hartlieb; Kai-Oliver Henrich; Konstantin Okonechnikov; Janine Altmüller; Peter Nürnberg; Steve Lefever; Bram de Wilde; Frederik Sand; Fakhera Ikram; Carolina Rosswog; Janina Fischer; Jessica Theissen; Falk Hertwig; Aatur D. Singhi; Thorsten Simon; Wenzel Vogel; Sven Perner; Barbara Krug; Matthias Schmidt; Sven Rahmann; Viktor Achter; Ulrich Lang; Christian Vokuhl; Monika Ortmann; Reinhard Büttner; Angelika Eggert; Frank Speleman; Roderick J. O’Sullivan; Roman K. Thomas; Frank Berthold; Jo Vandesompele; Alexander Schramm; Frank Westermann; Johannes H. Schulte; Martin Peifer; Matthias Fischer

doi:10.1126/science.aat6768

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A mechanistic classification of clinical phenotypes in neuroblastoma

Sandra Ackermann¹,²,*,
Maria Cartolano²,³,*,
Barbara Hero⁴,
Anne Welte¹,²,
Yvonne Kahlert¹,²,
Andrea Roderwieser¹,²,
Christoph Bartenhagen¹,²,
Esther Walter¹,²,
Judith Gecht⁴,
Laura Kerschke⁵,
Ruth Volland⁴,
Roopika Menon⁶,
Johannes M. Heuckmann⁶,
Moritz Gartlgruber⁷,
Sabine Hartlieb⁷,
Kai-Oliver Henrich⁷,
Konstantin Okonechnikov⁸,
Janine Altmüller²,⁹,
Peter Nürnberg²,⁹,¹⁰,
Steve Lefever¹¹,
Bram de Wilde¹¹,
Frederik Sand¹,²,
Fakhera Ikram¹,²,¹²,
Carolina Rosswog¹,²,
Janina Fischer¹,²,
Jessica Theissen¹,⁴,
Falk Hertwig¹,²,¹³,¹⁴,¹⁵,
Aatur D. Singhi¹⁶,
Thorsten Simon⁴,
Wenzel Vogel¹⁷,¹⁸,
Sven Perner¹⁷,¹⁸,
Barbara Krug¹⁹,
Matthias Schmidt²⁰,
Sven Rahmann²¹,²²,
Viktor Achter²³,
Ulrich Lang²³,²⁴,
Christian Vokuhl²⁵,
Monika Ortmann²⁶,
Reinhard Büttner²⁶,
Angelika Eggert¹³,¹⁴,¹⁵,
Frank Speleman¹¹,
Roderick J. O’Sullivan²⁷,
Roman K. Thomas³,¹⁴,²⁶,²⁸,
Frank Berthold⁴,*,
Jo Vandesompele¹¹,*,
Alexander Schramm²⁹,*,
Frank Westermann⁷,*,
Johannes H. Schulte¹³,¹⁴,¹⁵,²⁸,*,
Martin Peifer²,³,*,
Matthias Fischer¹,²,*,†

¹Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.
²Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
³Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, Cologne, Germany.
⁴Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.
⁵Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
⁶NEO New Oncology GmbH, Cologne, Germany.
⁷Division of Neuroblastoma Genomics (B087), German Cancer Research Center, and Hopp Children′s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.
⁸Division of Pediatric Neurooncology, German Cancer Research Center, and Hopp Children’s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.
⁹Cologne Center for Genomics, University of Cologne, Cologne, Germany.
¹⁰Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
¹¹Center for Medical Genetics, Ghent University, Ghent, Belgium.
¹²Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.
¹³Department of Pediatric Oncology and Hematology, Charité – Universitätsmedizin Berlin, Berlin, Germany.
¹⁴German Cancer Consortium (DKTK), Heidelberg, Germany.
¹⁵Berlin Institute of Health, Berlin, Germany.
¹⁶Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁷Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
¹⁸Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
¹⁹Department of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany.
²⁰Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
²¹Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
²²Computer Science, TU Dortmund, Dortmund, Germany.
²³Computing Center, University of Cologne, Cologne, Germany.
²⁴Department of Informatics, University of Cologne, Cologne, Germany.
²⁵Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany.
²⁶Department of Pathology, University of Cologne, Cologne, Germany.
²⁷Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute (UPCI), Hillman Cancer Center, Pittsburgh, PA, USA.
²⁸German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁹Department of Medical Oncology, West German Cancer Center Essen, University of Duisburg-Essen, Essen, Germany.

↵†Corresponding author. Email: matthias.fischer{at}uk-koeln.de

↵* These authors contributed equally to this work.

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Science 07 Dec 2018:
Vol. 362, Issue 6419, pp. 1165-1170
DOI: 10.1126/science.aat6768

Sandra Ackermann

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Maria Cartolano

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

3Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, Cologne, Germany.

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Barbara Hero

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Anne Welte

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Yvonne Kahlert

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Andrea Roderwieser

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Christoph Bartenhagen

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Esther Walter

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Judith Gecht

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Laura Kerschke

5Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.

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Ruth Volland

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Roopika Menon

6NEO New Oncology GmbH, Cologne, Germany.

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Johannes M. Heuckmann

6NEO New Oncology GmbH, Cologne, Germany.

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Moritz Gartlgruber

7Division of Neuroblastoma Genomics (B087), German Cancer Research Center, and Hopp Children′s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.

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Sabine Hartlieb

7Division of Neuroblastoma Genomics (B087), German Cancer Research Center, and Hopp Children′s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.

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Kai-Oliver Henrich

7Division of Neuroblastoma Genomics (B087), German Cancer Research Center, and Hopp Children′s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.

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Konstantin Okonechnikov

8Division of Pediatric Neurooncology, German Cancer Research Center, and Hopp Children’s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.

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Janine Altmüller

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

9Cologne Center for Genomics, University of Cologne, Cologne, Germany.

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Peter Nürnberg

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

9Cologne Center for Genomics, University of Cologne, Cologne, Germany.

10Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

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Steve Lefever

11Center for Medical Genetics, Ghent University, Ghent, Belgium.

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Bram de Wilde

11Center for Medical Genetics, Ghent University, Ghent, Belgium.

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Frederik Sand

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Fakhera Ikram

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

12Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan.

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Carolina Rosswog

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Janina Fischer

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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Jessica Theissen

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Falk Hertwig

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

13Department of Pediatric Oncology and Hematology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

14German Cancer Consortium (DKTK), Heidelberg, Germany.

15Berlin Institute of Health, Berlin, Germany.

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Aatur D. Singhi

16Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

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Thorsten Simon

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Wenzel Vogel

17Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

18Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.

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Sven Perner

17Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

18Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.

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Barbara Krug

19Department of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany.

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Matthias Schmidt

20Department of Nuclear Medicine, University of Cologne, Cologne, Germany.

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Sven Rahmann

21Genome Informatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

22Computer Science, TU Dortmund, Dortmund, Germany.

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Viktor Achter

23Computing Center, University of Cologne, Cologne, Germany.

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Ulrich Lang

23Computing Center, University of Cologne, Cologne, Germany.

24Department of Informatics, University of Cologne, Cologne, Germany.

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Christian Vokuhl

25Kiel Pediatric Tumor Registry, Department of Pediatric Pathology, University of Kiel, Kiel, Germany.

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Monika Ortmann

26Department of Pathology, University of Cologne, Cologne, Germany.

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Reinhard Büttner

26Department of Pathology, University of Cologne, Cologne, Germany.

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Angelika Eggert

13Department of Pediatric Oncology and Hematology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

14German Cancer Consortium (DKTK), Heidelberg, Germany.

15Berlin Institute of Health, Berlin, Germany.

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Frank Speleman

11Center for Medical Genetics, Ghent University, Ghent, Belgium.

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Roderick J. O’Sullivan

27Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute (UPCI), Hillman Cancer Center, Pittsburgh, PA, USA.

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Roman K. Thomas

3Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, Cologne, Germany.

14German Cancer Consortium (DKTK), Heidelberg, Germany.

26Department of Pathology, University of Cologne, Cologne, Germany.

28German Cancer Research Center (DKFZ), Heidelberg, Germany.

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Frank Berthold

4Department of Pediatric Oncology and Hematology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

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Jo Vandesompele

11Center for Medical Genetics, Ghent University, Ghent, Belgium.

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Alexander Schramm

29Department of Medical Oncology, West German Cancer Center Essen, University of Duisburg-Essen, Essen, Germany.

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Frank Westermann

7Division of Neuroblastoma Genomics (B087), German Cancer Research Center, and Hopp Children′s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany.

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Johannes H. Schulte

13Department of Pediatric Oncology and Hematology, Charité – Universitätsmedizin Berlin, Berlin, Germany.

14German Cancer Consortium (DKTK), Heidelberg, Germany.

15Berlin Institute of Health, Berlin, Germany.

28German Cancer Research Center (DKFZ), Heidelberg, Germany.

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Martin Peifer

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

3Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, Cologne, Germany.

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Matthias Fischer

1Department of Experimental Pediatric Oncology, University Children’s Hospital of Cologne, Medical Faculty, Cologne, Germany.

2Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

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For correspondence: matthias.fischer@uk-koeln.de

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A mechanistic classification of clinical phenotypes in neuroblastoma

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