Protein Structure Prediction and Bioinfamatic Analysis of Novel Fusion Gene IKZF1/Pfas in BPDCN

A novel fusion gene, IKAROS Family Zinc Finger 1 (IKZF1)/Phosphoribosylformylglycinamidine Synthase (PFAS), was identified in a patient diagnosed with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). Secondary protein structure analysis, 3D protein structure determination and domain analysis revealed loss of the ZnF-C2H2 domains of IKZF1 caused by premature translation termination at amino acid (AA) residue 55, which might cause dysfunction of IKZF1.

Bioinformatic analysis was conducted using RNA-seq data for 37 BPDCN samples from the GSE database (GSE62014 and GSE89565) to elucidate the role of IKZF1 in BPDCN. WGCNA showed that IKZF1 expression could be used to categorize BPDCN samples into two distinct clusters (IKZF1 ^high and IKZF1 ^low). Differentially expressed genes (DEGs) were identified in these two subgroups and subjected to GO and KEGG analyses. Mitochondrial function-related pathways and ubiquitin-mediated proteolysis were the most enriched pathways in the GO and KEGG analyses, respectively. A PPI network of the DEGs was constructed, and 10 key genes were identified (CSTF2, SF3B1, U2AF2, HNRNPH1, SF3B3, SNRNP200, LSM2, SLU7, CPSF4 and UPF3B). Most of these genes are related to tumorigenesis, cancer metastasis, and hematopoietic malignancies.

In conclusion, the novel IKZF1/PFAS fusion gene could cause dysfunction of the IKZF1. The bioinformatic analysis results emphasized the role of IKZF1 in BPDCN and identified 10 key genes closely related to IKZF1, most of which are tumorigenesis-related.