Integrative genomic analysis reveals cancer-associated mutations at the diagnosis of cancer in patients with ocular tumors

Abstract The genomic events associated with poor outcomes in other ocular tumors are poorly understood, except for the in-depth study of the retinoblastoma Rb gene. We investigated 48 patients with ocular tumors, using three types of samples - cancerous tissue, paraneoplastic tissue, and peripheral blood. We employed combined exome and transcriptome analysis to search for high-frequency mutated genes and susceptibility genes in ocular tumors. Our exon sequencing analysis identified four clear causative genes ( TP53, PTCH1, SMO, BAP1 ), most of which were associated with basal cell carcinoma. Two mutations in BAP1 were clearly associated with choroidal melanoma, and no clear causative loci were found in other cancer types. Our susceptibility gene analysis identified hotspot genes such as RUNX1, APC, IDH2 , and BRCA2 . High-frequency gene analysis identified TP53 , TTN , and MUC16 genes, among others. Transcriptome analysis identified TOP2A and ZWINT genes were upregulated in all samples, while CFD , ELANE , HBA1 , and HBB were downregulated. Our KEGG enrichment analysis indicated that the PI3K-Akt signaling pathway and transcriptional misregulation in cancer may be involved in the process of ocular tumorigenesis. We found that TP53 is clearly involved in ocular tumorigenesis, especially in basal cell carcinoma, and its PI3K-Akt signaling pathway may be an essential pathway involved in ocular tumorigenesis. Additionally, RUNX1 , SMO , TOP2A , and ZWINT are highly likely to be involved in ocular tumorigenesis, and subsequent functional experiments can be carried out to verify the mechanisms of these genes in regulating tumorigenesis.