Whole-exome sequencing and immunohistochemistry findings in von Hippel-Lindau disease.
Mol Genet Genomic Med
; 7(9): e880, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31317677
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Imuno-Histoquímica
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Proteína Supressora de Tumor Von Hippel-Lindau
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Sequenciamento do Exoma
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Doença de von Hippel-Lindau
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article