Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway;
Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Cancer Genomics Proteomics. 2024 May-Jun;21(3):252-259. doi: 10.21873/cgp.20444.
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.
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.
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.
背景/目的：“钙化性软骨性间叶性肿瘤”一词于 2021 年引入，用于描述一组具有多种形态特征的肿瘤，包括软骨或软骨样基质的形成。这些肿瘤经常携带嵌合基因，其中 5'端伙伴基因是纤维连接蛋白 1，3'端伙伴基因编码受体酪氨酸激酶。我们的研究探讨了在钙化性软骨性间叶性肿瘤中血小板衍生生长因子受体α（PDGFRA）和泛素特异性肽酶 8（USP8）基因的融合。
对位于 71 岁女性腿部的肿瘤进行了基因研究。短期培养的肿瘤细胞的 G 带分析显示核型为 46,XX,t(4;15)(q12;q21)[6]/46,XX[4]。RNA 测序检测到 PDGFRA::USP8 和 USP8::PDGFRA 嵌合转录本，通过 RT-PCR/Sanger 测序进行了验证。PDGFRA::USP8 嵌合蛋白预测具有细胞膜定位和作为嵌合泛素水解酶的功能。USP8::PDGFRA 蛋白预测为核定位，作为细胞代谢过程的正向调节剂。
我们首次报道了一例携带平衡 t(4;15)(q12;q21)染色体易位的钙化性软骨性间叶性肿瘤，导致产生 PDGFRA::USP8 和 USP8::PDGFRA 嵌合体。PDGFRA::USP8 蛋白位于细胞膜上，作为 PDGFs 激活的嵌合泛素水解酶发挥作用。相反，USP8::PDGFRA 是一种核蛋白，调节代谢过程。
