COL1A1–PDGFB Fusion Gene Detection Through Bulk RNA-Seq and Transcriptomic Features of Dermatofibrosarcoma Protuberans

Abstract

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with obscure origin and multidirectional differentiation. Application of RNA-Seq in the detection of COL1A1–PDGFB is still at early stages. OBJECTIVE We aim to test the efficacy of fusion gene detection using bulk RNA-Seq in DFSPs, explore altered molecular pathways and biological processes for evidences of tumor origin and cell identity shift. MATERIALS AND METHODS Dermatofibrosarcoma protuberans and normal dermis samples were acquired for RNA-Seq. Fusion gene detection was performed using STAR-Fusion. RNA-Seq 2G yielded differentially expressed genes. Altered pathways, key gene ontology terms, and similar cell/tissue types were identified with gene set enrichment analysis. xCell was used for cell types enrichment analysis. RESULTS 28/30 CD34(+) cases were positive for COL1A1–PDGFB. 406 upregulated and 543 downregulated genes were determined. Among the top 10 upregulated genes, 6 had neural distribution, function, or disease correlation. The upregulated genes were related to synapse, trans-synaptic signaling, neural development, and extracellular matrix. Similarities between DFSP and nervous system components were highlighted, with fibroblast cellular abundancy increased during xCell analysis. CONCLUSION Bulk RNA-Seq provided with high detection rate of COL1A1-PDGFB. Dermatofibrosarcoma protuberans showed fibroblastic activity and neural features, which validated DFSP's fibroblast origin and tendency of neural differentiation.