{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:30:13Z","timestamp":1774330213232,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T00:00:00Z","timestamp":1563321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603157"],"award-info":[{"award-number":["81603157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>von Hippel\u2013Lindau (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\u2010related tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome 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\u2010nucleotide 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hemangioblastomas and two renal cell carcinomas were sequenced. The bioinformatics analysis revealed a <jats:italic>VHL<\/jats:italic> somatic variant in all tumors; no other SNV was detected. Immunohistochemistry showed the abnormal expression of the phospho\u2010S6 ribosomal protein in the hemangioblastomas, but not in the renal clear cell carcinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Except for a SNV in the <jats:italic>VHL<\/jats:italic> gene, no other somatic SNVs were detected using WES. The phospho\u2010S6 ribosomal protein in the mTOR pathway is a potential target in VHL\u2010related cerebellum hemangioblastomas.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.880","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T04:25:26Z","timestamp":1563423926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole\u2010exome sequencing and immunohistochemistry findings in von Hippel\u2013Lindau disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-5560","authenticated-orcid":false,"given":"Xiaopeng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiafei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of General Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Guo","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Corelabs Beijing P.R. China"},{"name":"Clinical Bio\u2010bank Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyu","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Pathology Xinxiang Medical University First Affiliated Hospital Weihui P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoman","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing P.R. 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