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Akihiro Ikeda, Tetsuya Takimoto, Kazuya Oikawa, Sakae Ikeda, Gillian J McLellan, Nader Sheibani, Richard Dubielzig, Daniel Albert; Genomic analysis of cat lens and lens tumor. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3630.
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© ARVO (1962-2015); The Authors (2016-present)
Malignant tumors in the lens occur most commonly in cats following lens trauma and comprise 3.3% of intraocular and adnexal neoplasm. On the other hand, no case of lens tumor has been reported so far in humans. The purpose of this study is 1) to understand the nature of cat normal lens compared with that of humans by gene expression analysis and 2) to characterize tumor-specific mutations in cat lens tumor tissues.
RNAseq analysis was performed using normal cat lens. The data from this analysis were compared with gene expression data for human lens epithelial cells and cortical fiber cells obtained from public database. In order to identify tumor-specific mutations, we performed whole exome sequence analysis using both lens tumor tissues and normal (non-tumor) tissues from the same donor cats (n=5). By comparing sequences from lens tumor and normal tissues, we identified tumor-specific mutations.
In gene expression analysis, hierarchical clustering analysis showed that the pattern of gene expression in cat lens was significantly different from that of human cells derived from lens. GO term analysis showed that terms related with immunity were significantly enriched in genes expressed at lower levels in cat lens compared to human lens cells. KEGG pathway analysis indicated that genes involved in various signaling pathways were enriched in cat lens. Genes involved in Wnt signaling pathway were significantly enriched in genes expressed at higher levels in cat genes. By exome sequencing, we identified a single gene, zinc finger protein 114 (ZNF114), that had a mutation (Indel) in all five tumor tissues but not in any of the normal tissues, indicating that the mutation was somatically acquired. All ZNF114mutations occurred at the beginning of the start codon and four of them were exactly the same insertion. Eight other genes carried tumor-specific mutations in four tumor tissues.
This study showed that Wnt signaling is upregulated in normal cat lens. We hypothesize that cat lens cells are predisposed to proliferation in response to extracellular stimuli such as an increase in ligands for Wnt signaling during wound healing. The ZNF114 gene that was mutated in all lens tumor tissues may be a cancer driver gene.
This is a 2020 ARVO Annual Meeting abstract.
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