Open AccessWhole‐exome sequencing and immunohistochemistry findings in von Hippel–Lindau disease
Author(s) -
Guo Xiaopeng,
Gao Lu,
Hong Xiafei,
Guo Dan,
Di Wenyu,
Wang Xiaoman,
Xu Zhiqin,
Xing Bing
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.880
Subject(s) - von hippel–lindau disease , sanger sequencing , immunohistochemistry , exome sequencing , biology , carcinogenesis , pathology , somatic cell , cancer research , disease , medicine , cancer , gene , genetics , dna sequencing , mutation
Abstract 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.