{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:30:15Z","timestamp":1774330215964,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,10,31]],"date-time":"2005-10-31T00:00:00Z","timestamp":1130716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>von Hippel\u2013Lindau (VHL) disease is caused by germline mutations of the <jats:italic>VHL<\/jats:italic> tumor suppressor gene. Affected individuals are predisposed to development of multiple neoplastic and preneoplastic lesions of different organs. A \u201csecond hit,\u201d which is usually represented by deletion in the wild\u2010type <jats:italic>VHL<\/jats:italic> allele at 3p25, is necessary for initiation of tumor formation. The impact of the size of this deletion is thought to be critical, because other tumor suppressor genes are located nearby, but this has not yet been studied in detail. We mapped the deletion size of the \u201csecond hit\u201d in microdissected tissue from 16 different VHL\u2010associated lesions from the same patient using 10 polymorphic chromosome 3 markers. We found that the deletion size is highly variable, ranging from short deletions around the <jats:italic>VHL<\/jats:italic> gene to complete loss of the chromosome 3. The deletion sizes are not correlated with the site of the germline mutation, the affected organ, or the type or biological behavior of the tumor. Even preneoplastic cystic structures may harbor entire loss of the chromosome 3, suggesting that loss of VHL gene function alone is not immediately causative for neoplastic growth, but further events, either mutations and deletions in other chromosomes or epigenetic or other than genetic phenomena, are required for tumor formation. 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