title: A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells.
abstract: Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are related conditions with features of both reactive inflammatory disorders and clonal neoplastic proliferations. Chromosomal translocations involving chromosome 1p13 have been reported in both TGCT and PVNS. We confirm that translocations involving 1p13 are present in a majority of cases of TGCT and PVNS and show that CSF1 is the gene at the chromosome 1p13 breakpoint. In some cases of both TGCT and PVNS, CSF1 is fused to COL6A3 (2q35). The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.
authors.affiliation: Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Miller
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Gulsah
authors.initials: G
authors.lastname: Kaygusuz
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Marinelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
mesh_terms: D002465:Cell Movement / Q000235:genetics; D002878:Chromosomes, Human, Pair 1; D002889:Chromosomes, Human, Pair 2; D024142:Collagen Type VI / Q000235:genetics; D005819:Genetic Markers; D005870:Giant Cell Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000473:pathology*; D013586:Synovitis, Pigmented Villonodular / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D024142:Collagen Type VI; D005819:Genetic Markers; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor