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ResearchIn-Press PreviewGeneticsOncology Open Access | 10.1172/jci.insight.146351

Chromosome 8 gain is associated with high-grade transformation in MPNST

Carina A. Dehner,1 Chang In Moon,2 Xiyuan Zhang,3 Zhaohe Zhou,2 Christopher A. Miller,5 Hua Xu,6 Xiaodan Wan,7 Kuangying Yang,2 R. Jay Mashl,2 Sara J.C. Gosline,8 Yuxi Wang,2 Xiaochun Zhang,2 Abigail Godec,2 Paul A. Jones,2 Sonika Dahiya,1 Himanshi Bhatia,2 Tina Primeau,2 Shunqiang Li,9 Kai Pollard,10 Fausto J. Rodriguez,11 Li Ding,2 Christine A. Pratilas,10 Jack F. Shern,12 and Angela C. Hirbe13

1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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1Department of Pathology and Immunology, Washington University, St. Louis, St. Louis, United States of America

2Department of Internal Medicine, Washington University, St. Louis, St. Louis, United States of America

3Pediatric Oncology Branch, National Institute of Health, Bethesda, United States of America

4Department of Internal Medicine, Washington University, St. Louis, St Louis, United States of America

5Department of Internal Medicine, McDonnell Genome Institute, St. Louis, United States of America

6Department of Cardiothoracic Surgery, The First Affiliated Hospital, Nanchang University, Nangchang, China

7Department of Electrocardiograph, The First Affiliated Hospital, Nanchang University, Nanchang, China

8Pacific Northwest National Laboratory, Seattle, United States of America

9Washington University, St. Louis, St. Louis, United States of America

10Division of Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America

11Department of Pathology, Johns Hopkins University Medical Center, Baltimore, United States of America

12Pediatric Oncology Branch, National Institutes of Health, Bethesda, United States of America

13Department of Internal Medicine, Washington University in St Louis, St. Louis, United States of America

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Published February 16, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.146351.
Copyright © 2021, Dehner 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 February 16, 2021 - Version history
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Abstract

One of the most common malignancies affecting adults with Neurofibromatosis type 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST), an aggressive and often fatal sarcoma which commonly arises from benign plexiform neurofibromas. Despite advances in our understanding of MPNST pathobiology, there are few effective therapeutic options, and no investigational agents have proven success in clinical trials. To further understand the genomic heterogeneity of MPNST, and to generate a preclinical platform that encompasses this heterogeneity, we developed a collection of NF1-MPNST patient-derived xenografts (PDX). These PDX were compared to the primary tumors from which they were derived using copy number analysis, whole-exome and RNA sequencing. We identified chromosome 8 gain as a recurrent genomic event in MPNST and validated its occurrence by FISH in the PDX and parental tumors, in a validation cohort, and by single cell sequencing in the PDX. Finally, we show that chromosome 8 gain is associated with inferior overall survival in soft tissue sarcomas. Taken together, these data suggest that chromosome 8 gain is a critical event in MPNST pathogenesis, and may account for the aggressive nature and poor outcomes in this sarcoma subtype.

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