PT  - JOURNAL ARTICLE
AU  - PANAGOPOULOS, IOANNIS
AU  - ANDERSEN, KRISTIN
AU  - GORUNOVA, LUDMILA
AU  - LOBMAIER, INGVILD
TI  - Fusion of Platelet Derived Growth Factor Receptor Alpha (<em>PDGFRA</em>) With Ubiquitin Specific Peptidase 8 (<em>USP8</em>) in a Calcified Chondroid Mesenchymal Neoplasm Harboring t(4;15)(q12;q21) as a Sole Aberration
AID  - 10.21873/cgp.20444
DP  - 2024 May 01
TA  - Cancer Genomics - Proteomics
PG  - 252--259
VI  - 21
IP  - 3
4099  - http://cgp.iiarjournals.org/content/21/3/252.short
4100  - http://cgp.iiarjournals.org/content/21/3/252.full
SO  - Cancer Genomics Proteomics2024 May 01; 21
AB  - Background/Aim: The term “calcified chondroid mesenchymal neoplasm” was introduced in 2021 to describe a group of tumors characterized by various morphological features, including the formation of cartilage or chondroid matrix. These tumors frequently carry chimeric genes where the 5′-end partner gene is fibronectin 1 and the 3′-end partner gene codes for receptor tyrosine kinase. Our study explores fusion of the genes platelet-derived growth factor receptor alpha (PDGFRA) and ubiquitin-specific peptidase 8 (USP8) in calcified chondroid mesenchymal neoplasm. Case Report: Genetic investigations were conducted on a tumor located in the leg of a 71-year-old woman. G-banding analysis of short-term cultured tumor cells revealed the karyotype 46,XX,t(4;15)(q12;q21)[6]/46,XX[4]. RNA sequencing detected in-frame PDGFRA::USP8 and USP8::PDGFRA chimeric transcripts, which were validated by RT-PCR/Sanger sequencing. The PDGFRA::USP8 chimeric protein is predicted to have cell membrane location and functions as a chimeric ubiquitinyl hydrolase. The USP8::PDGFRA protein was predicted to be nuclear and function as a positive regulator of cellular metabolic process. Conclusion: We report, for the first time, a calcified chondroid mesenchymal neoplasm carrying a balanced t(4;15)(q12;q21) chromosomal translocation, resulting in the generation of both PDGFRA::USP8 and USP8::PDGFRA chimeras. The PDGFRA::USP8 protein is located on the cell membrane and functions as a chimeric ubiquitinyl hydrolase, activated by PDGFs. Conversely, USP8::PDGFRA is a nuclear protein regulating metabolic processes.