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ResearchIn-Press PreviewGeneticsOncology Open Access | 10.1172/JCI187627

High 4E-BP-1 expression associates with chromosome 8 gain and CDK4/6 sensitivity in Ewing Sarcoma

Cornelius M. Funk,1 Anna C. Ehlers,1 Martin F. Orth,2 Karim Aljakouch,3 Jing Li,1 Tilman L.B. Hoelting,1 Rainer Will,4 Florian H. Geyer,1 A. Katharina Ceranski,1 Franziska Willis,5 Endrit Vinca,1 Shunya Ohmura,1 Roland Imle,6 Jana Siebenlist,1 Angelina Yershova,1 Maximilian M.L. Knott,7 Felina Zahnow,8 Ana Sastre,9 Javier Alonso,10 Felix Sahm,11 Heike Peterziel,12 Anna Loboda,12 Martin Schneider,5 Ana Banito,6 Gabriel Leprivier,13 Wolfgang Hartmann,14 Uta Dirksen,15 Olaf Witt,16 Ina Oehme,16 Stefan M. Pfister,17 Laura Romero-Pérez,1 Jeroen Krijgsveld,3 Florencia Cidre-Aranaz,1 Thomas G.P. Grünewald,1 and Julian Musa1

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Funk, C. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Ehlers, A. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Orth, M. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Aljakouch, K. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Li, J. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Hoelting, T. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Will, R. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Geyer, F. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Ceranski, A. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Willis, F. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Vinca, E. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Ohmura, S. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Imle, R. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Siebenlist, J. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Yershova, A. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Knott, M. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Find articles by Zahnow, F. in: PubMed | Google Scholar

1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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1Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Patholo, LMU Munich, Munich, Germany

3Division of Proteomics of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

4Cellular Tools Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany

5Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany

6Soft-Tissue Sarcoma Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

7Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany

8Hopp-Children’s Cancer Center (KiTZ), Heidelberg, Germany

9Unidad Hemato-oncología Pediátrica, Hospital Infantil Universitario La Paz, Madrid, Spain

10Pediatric Solid Tumour Laboratory, Institute of Rare Diseases Research (IIE, Instituto de Salud Carlos III, Madrid, Spain

11Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

12Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany

13Institute of Neuropathology, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany

14Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany

15Pediatrics III, West German Cancer, University Hospital of Essen, Essen, Germany

16Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

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Published October 16, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI187627.
Copyright © 2025, Funk et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 16, 2025 - Version history
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Abstract

Chromosome 8 (chr8) gains are common in cancer, but their contribution to tumor heterogeneity is largely unexplored. Ewing sarcoma (EwS) is defined by FET::ETS fusions with few other recurrent mutations to explain clinical diversity. In EwS, chr8 gains are the second most frequent alteration, making it an ideal model to study their relevance in an otherwise silent genomic context. We report that chr8 gain-driven expression patterns correlate with poor overall survival of EwS patients. This effect is mainly mediated by increased expression of the translation initiation factor binding protein 4E-BP1, encoded by EIF4EBP1 on chr8. Among all chr8-encoded genes, EIF4EBP1 expression showed the strongest association with poor survival and correlated with chr8 gains in EwS tumors. Similar findings emerged across multiple TCGA cancer entities. Multi-omics profiling revealed that 4E-BP1 orchestrates a pro-proliferative proteomic network. Silencing 4E-BP1 reduced proliferation, clonogenicity, spheroidal growth in vitro, and tumor growth in vivo. Drug screens demonstrated that high 4E-BP1 expression sensitizes EwS to pharmacological CDK4/6-inhibition. Chr8 gains and elevated 4E-BP1 emerge as prognostic biomarkers in EwS, with poor outcomes driven by 4E-BP1-mediated pro-proliferative networks that sensitize tumors to CDK4/6 inhibitors. Testing for chr8 gains may enhance risk stratification and therapy in EwS and other cancers.

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