Expanding the spectrum of tyrosine kinase fusions in calcified chondroid mesenchymal neoplasms: Identification of a novel PDGFRA::USP8 gene fusion

Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologic...

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Bibliographic Details
Published in:Genes chromosomes & cancer 2024-01, Vol.63 (1), p.e23197-n/a
Main Authors: Fisher, Yael, Lacambra, Maribel D., Almohsen, Shahd S., Chow, Chit, Hornick, Jason L., To, Ka‐Fai, Dickson, Brendan C.
Format: Article
Language:English
Subjects:
Calcification
calcified chondroid mesenchymal neoplasm
FGFR
FN1
Gene fusion
Gene rearrangement
Kinases
NTRK
PDGFRA
Protein-tyrosine kinase
soft tissue chondroma
Stellate cells
Tumors
tyrosine kinase
USP8
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Summary:Calcified chondroid mesenchymal neoplasms represent a distinct, and recently recognized, spectrum of tumors. To date most cases have been reported to be characterized by FN1 gene fusions involving multiple potential tyrosine kinase partners. Following incidental identification of a tumor morphologically corresponding to calcified chondroid mesenchymal neoplasm, but with a PDGFRA::USP8 gene fusion, we undertook a retrospective review to identify and characterize additional such cases. A total of four tumors were identified. Each was multilobulated and composed of polygonal‐epithelioid‐stellate cells with a background of chondroid matrix containing distinctive patterns of calcification. Targeted RNA sequencing revealed an identical PDGFRA (exon 22)::USP8 (exon 5) gene fusion in each case. Subsequent immunohistochemical staining confirmed the presence of PDGFRα overexpression. In summary, we report a series of four tumors within the morphologic spectrum of calcified chondroid mesenchymal neoplasms. In contrast to prior reports, these tumors harbored a novel PDGFRA::USP8 gene fusion, rather than FN1 rearrangement. Our findings expand the molecular diversity of these neoplasms, and suggest they are united through activation of protein kinases.
ISSN:1045-2257
1098-2264
1098-2264
DOI:10.1002/gcc.23197