PDF(Pubmed)
Abstract：
OBJECTIVE: Apart from the role of the retinoblastoma gene, the genomic events associated with poor outcomes in patients with ophthalmic tumors are poorly understood.
METHODS: We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis.
RESULTS: We identified four clearly causative genes (TP53, PTCH1, SMO, BAP1). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2, and BRCA2, and high-frequency gene analysis identified several genes, including TP53, TTN, and MUC16. Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD, ELANE, HBA1, and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis.
CONCLUSIONS: TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A, and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.
METHODS: We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis.
RESULTS: We identified four clearly causative genes (TP53, PTCH1, SMO, BAP1). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2, and BRCA2, and high-frequency gene analysis identified several genes, including TP53, TTN, and MUC16. Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD, ELANE, HBA1, and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis.
CONCLUSIONS: TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A, and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.
摘要：
目的：除了视网膜母细胞瘤基因的作用外，与眼科肿瘤患者预后不良相关的基因组事件尚不清楚.
方法：我们回顾性分析了48例六种类型的眼科肿瘤患者。我们使用联合外显子组和转录组分析在这些患者中搜索高频突变基因和易感基因。
结果：我们确定了四个明显的致病基因（TP53，PTCH1，SMO，BAP1).易感性基因分析确定热点基因，包括RUNX1、APC、IDH2和BRCA2，高频基因分析确定了几个基因，包括TP53，TTN，MUC16转录组分析确定了5868个差异表达基因，其中TOP2A和ZWINT在所有样品中上调，而CFD,伊兰,HBA1和HBB下调。《京都基因百科全书》和基因组富集分析表明，癌症信号通路中的磷酸肌醇3-激酶（PI3K）-Akt和转录失调可能与眼科肿瘤发生有关。
结论：TP53明显参与眼科肿瘤发生，尤其是基底细胞癌，PI3K-Akt信号通路可能是参与眼科肿瘤发生的重要通路。RUNX1,SMO,TOP2A,ZWINT也很可能参与眼科肿瘤发生，但是需要进一步的功能实验来验证这些基因在调节肿瘤发生中的机制。
方法：我们回顾性分析了48例六种类型的眼科肿瘤患者。我们使用联合外显子组和转录组分析在这些患者中搜索高频突变基因和易感基因。
结果：我们确定了四个明显的致病基因（TP53，PTCH1，SMO，BAP1).易感性基因分析确定热点基因，包括RUNX1、APC、IDH2和BRCA2，高频基因分析确定了几个基因，包括TP53，TTN，MUC16转录组分析确定了5868个差异表达基因，其中TOP2A和ZWINT在所有样品中上调，而CFD,伊兰,HBA1和HBB下调。《京都基因百科全书》和基因组富集分析表明，癌症信号通路中的磷酸肌醇3-激酶（PI3K）-Akt和转录失调可能与眼科肿瘤发生有关。
结论：TP53明显参与眼科肿瘤发生，尤其是基底细胞癌，PI3K-Akt信号通路可能是参与眼科肿瘤发生的重要通路。RUNX1,SMO,TOP2A,ZWINT也很可能参与眼科肿瘤发生，但是需要进一步的功能实验来验证这些基因在调节肿瘤发生中的机制。
