A mechanistic classification of clinical phenotypes in neuroblastoma

Author:

Ackermann Sandra12ORCID,Cartolano Maria23,Hero Barbara4ORCID,Welte Anne12,Kahlert Yvonne12,Roderwieser Andrea12,Bartenhagen Christoph12,Walter Esther12,Gecht Judith4,Kerschke Laura5ORCID,Volland Ruth4,Menon Roopika6ORCID,Heuckmann Johannes M.6ORCID,Gartlgruber Moritz7,Hartlieb Sabine7,Henrich Kai-Oliver7,Okonechnikov Konstantin8,Altmüller Janine29,Nürnberg Peter2910ORCID,Lefever Steve11,de Wilde Bram11ORCID,Sand Frederik12,Ikram Fakhera1212,Rosswog Carolina12,Fischer Janina12,Theissen Jessica14,Hertwig Falk12131415ORCID,Singhi Aatur D.16,Simon Thorsten4,Vogel Wenzel1718,Perner Sven1718,Krug Barbara19,Schmidt Matthias20,Rahmann Sven2122ORCID,Achter Viktor23,Lang Ulrich2324,Vokuhl Christian25,Ortmann Monika26,Büttner Reinhard26,Eggert Angelika131415ORCID,Speleman Frank11,O’Sullivan Roderick J.27,Thomas Roman K.3142628,Berthold Frank4,Vandesompele Jo11,Schramm Alexander29ORCID,Westermann Frank7ORCID,Schulte Johannes H.13141528,Peifer Martin23,Fischer Matthias12

Affiliation:

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

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

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

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

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

6. NEO New Oncology GmbH, Cologne, Germany.

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

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

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

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

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

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

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

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

15. Berlin Institute of Health, Berlin, Germany.

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

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

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

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

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

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

22. Computer Science, TU Dortmund, Dortmund, Germany.

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

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

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

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

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

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

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

Abstract

A systematic look at a childhood tumor Neuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly variable. Some neuroblastomas are fatal despite treatment, whereas others respond well to treatment and some undergo spontaneous regression without treatment. Ackermann et al. sequenced more than 400 pretreatment neuroblastomas and identified molecular features that characterize the three distinct clinical outcomes. Low-risk tumors lack telomere maintenance mechanisms, intermediate-risk tumors harbor telomere maintenance mechanisms, and high-risk tumors harbor telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Science , this issue p. 1165

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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