Whole-exome sequencing and immunohistochemistry findings in von Hippel-Lindau disease
Whole-exome sequencing and immunohistochemistry findings in von Hippel-Lindau disease
复制标题
冯·希佩尔-林道病的全外显子组测序和免疫组织化学研究结果
DOI：
10.1002/mgg3.880
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发表时间：
2019-07-17
影响因子：
2
通讯作者：
Xing, Bing
中科院分区：
文献类型：
--
作者：
Guo, Xiaopeng;Gao, Lu;Xing, Bing
背景：von Hippel-Lindau病（VHL）是一种遗传性常染色体显性遗传病，一个患者的多个器官可发生多个肿瘤。然而，肿瘤发生的确切机制尚不清楚，需要进一步的研究来阐明不同VHL相关肿瘤是否涉及相同的信号通路。方法对一个VHL家系的肿瘤标本和配对外周血标本进行全外显子组测序。进行生物信息学分析以鉴定存在于所有肿瘤组织中的候选体细胞单核苷酸变体（SNV）。然后使用桑格测序来验证使用WES鉴定的SNV。进行免疫组织化学以分析在肿瘤组织中异常激活的mTOR通路的组分。结果2例血管母细胞瘤和2例肾细胞癌获得测序结果。生物信息学分析揭示了所有肿瘤中的VHL体细胞变异;未检测到其他SNV。免疫组化显示磷酸化S6核糖体蛋白在肾血管母细胞瘤中异常表达，而在肾透明细胞癌中无异常表达。结论除VHL基因的SNV外，WES法未检测到其他体细胞SNV。mTOR通路中的磷酸化S6核糖体蛋白是VHL相关小脑血管母细胞瘤的潜在靶点。
Background von Hippel-Lindau (VHL) disease has a hereditary, autosomal dominant pattern, and multiple tumors can develop in multiple organs of a single patient. However, the exact mechanisms of tumorigenesis are unclear, and further studies are needed to clarify whether the same signaling pathways are involved in different VHL-related tumors. Methods Whole-exome sequencing (WES) of tumor and paired peripheral blood samples were performed for a VHL disease pedigree. A bioinformatics analysis was conducted to identify candidate somatic single-nucleotide variants (SNVs) present in all tumor tissues. Sanger sequencing was then used to validate the SNVs identified using WES. Immunohistochemistry was performed to analyze components of the mTOR pathway, which was abnormally activated in tumor tissues. Results Two hemangioblastomas and two renal cell carcinomas were sequenced. The bioinformatics analysis revealed a VHL somatic variant in all tumors; no other SNV was detected. Immunohistochemistry showed the abnormal expression of the phospho-S6 ribosomal protein in the hemangioblastomas, but not in the renal clear cell carcinomas. Conclusion Except for a SNV in the VHL gene, no other somatic SNVs were detected using WES. The phospho-S6 ribosomal protein in the mTOR pathway is a potential target in VHL-related cerebellum hemangioblastomas.