Data from Interactions in CSF1-Driven Tenosynovial Giant Cell Tumors

Abstract

AbstractPurpose: A major component of cells in tenosynovial giant cell tumor (TGCT) consists of bystander macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. An autocrine loop was postulated where the neoplastic cells would be stimulated through CSF1R expressed on their surface. Here, we use single-cell RNA sequencing (scRNA-seq) to investigate cellular interactions in TGCT. Experimental Design: A total of 18,788 single cells from three TGCT and two giant cell tumor of bone (GCTB) samples underwent scRNA-seq. The three TGCTs were additionally analyzed using long-read RNA sequencing. Immunofluorescence and IHC for a range of markers were used to validate and extend the scRNA-seq findings. Results: Two recurrent neoplastic cell populations were identified in TGCT that are highly similar to nonneoplastic synoviocytes. We identified GFPT2 as a marker that highlights the neoplastic cells in TCGT. We show that the neoplastic cells themselves do not express CSF1R. We identified overlapping MAB features between the giant cells in TGCT and GCTB. Conclusions: The neoplastic cells in TGCT are highly similar to nonneoplastic synoviocytes. The lack of CSF1R on the neoplastic cells indicates they may be unaffected by current therapies. High expression of GFPT2 in the neoplastic cells is associated with activation of the YAP1/TAZ pathway. In addition, we identified expression of the platelet-derived growth factor receptor in the neoplastic cells. These findings suggest two additional pathways to target in this tumor.

Authors 16

1. David G.P. van IJzendoorn

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, California

2. Magdalena Matusiak

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, California

3. Gregory W. Charville

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, California

4. Geert Spierenburg Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, the Netherlands

5. Sushama Varma

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, California

6. Deana R.C. Colburg

   Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology, Stanford University School of Medicine, Stanford, California

7. Michiel A. J. van de Sande Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, the Netherlands

8. Kirsten van Langevelde Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands

9. David Glenn Mohler

   Stanford University

   Affiliation as printed

   Department of Orthopedic Surgery, Stanford University, Stanford, California

10. Kristen N. Ganjoo

    Stanford Medicine · Stanford University

    Affiliation as printed

    Division of Oncology, Department of Medicine, Stanford University, Stanford, California

11. Nam Q. Bui

    Stanford Medicine · Stanford University

    Affiliation as printed

    Division of Oncology, Department of Medicine, Stanford University, Stanford, California

12. Raffi S. Avedian

    Stanford University

    Affiliation as printed

    Department of Orthopedic Surgery, Stanford University, Stanford, California

13. Judith V.M.G. Bovée Aachen Department of Pathology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands

14. Robert J. Steffner

    Stanford University

    Affiliation as printed

    Department of Orthopedic Surgery, Stanford University, Stanford, California

15. Robert B. West

    Stanford Medicine · Stanford University

    Affiliation as printed

    Department of Pathology, Stanford University School of Medicine, Stanford, California

16. Matt van de Rijn

    Stanford Medicine · Stanford University

    Affiliation as printed

    Department of Pathology, Stanford University School of Medicine, Stanford, California