{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:13:29Z","timestamp":1786698809113,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T00:00:00Z","timestamp":1082937600000},"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":[[2004,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The histogenetic origin and the basis of the distribution of central nervous system (CNS) hemangioblastomas in the von Hippel\u2013Lindau (VHL) tumor suppressor gene syndrome, VHL disease, are unknown. To better understand hemangioblastoma histogenesis, we analyzed postmortem CNS tissues from four patients with well\u2010established diagnosis of VHL disease including development of characteristic tumors and positive family history. Numerous angiomesenchymal tumorlets, which resembled hemangioblastoma, but which also consistently showed distinct histological features, were distributed in the nerve roots, spinal cord, and cerebellum. Genetic analysis consistently showed deletion of the wild\u2010type VHL allele in these tumorlets. Most angiomesenchymal tumorlets were in the dorsal nerve roots; the anterior roots and cerebellum were less frequently affected. Tumorlet distribution was highly consistent in the four cases. In analogy to the wide morphological spectrum of lesions known to exist in VHL kidneys, nerve roots appear to harbor more wide\u2010spread and morphologically heterogeneous changes than previously appreciated. The abundance of tumorlets, associated with highly consistent morphology and topography, suggests a developmental origin of hemangioblastoma. Therefore, in VHL disease, inactivation of the VHL wild\u2010type allele appears necessary, but not sufficient, for the formation of tumor that produces symptoms and neurological disability.<\/jats:p>","DOI":"10.1002\/ana.20090","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T18:01:36Z","timestamp":1083002496000},"page":"721-728","source":"Crossref","is-referenced-by-count":43,"title":["Developmental effects of von Hippel\u2013Lindau gene deficiency"],"prefix":"10.1002","volume":"55","author":[{"given":"Alexander O.","family":"Vortmeyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quingyang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn\u2010Soo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward H.","family":"Oldfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,4,26]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197502)35:2<326::AID-CNCR2820350206>3.0.CO;2-8"},{"key":"e_1_2_6_3_2","first-page":"1358","article-title":"Up\u2010regulation of vascular endothelial growth factor and its receptors in von Hippel\u2010Lindau disease\u2010associated and sporadic hemangioblastomas","volume":"55","author":"Wizigmann\u2010Voos S","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_6_4_2","first-page":"763","article-title":"Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas","volume":"148","author":"Hatva E","year":"1996","journal-title":"Am J Pathol"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(97)90075-7"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.159.6.1442389"},{"key":"e_1_2_6_7_2","first-page":"620","article-title":"A microdissection technique for archival DNA analysis of specific cell populations in lesions less than 1 mm in size","volume":"146","author":"Zhuang Z","year":"1995","journal-title":"Am J Pathol"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00071-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(02)00010-2"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.2-4-356"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.98.1.0082"},{"key":"e_1_2_6_12_2","first-page":"271","article-title":"Histogenesis of stromal cells in cerebellar hemangioblastomas. An immunohistochemical study","volume":"134","author":"Becker I","year":"1989","journal-title":"Am J Pathol"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.3171\/spi.2003.99.1.0064"},{"key":"e_1_2_6_14_2","first-page":"363","article-title":"Discussion on vascular tumors of the brain and spinal cord","volume":"24","author":"Lindau A","year":"1931","journal-title":"Proc R Soc Med"},{"key":"e_1_2_6_15_2","first-page":"7051","article-title":"Developmental arrest of angioblastic lineage initiates tumorigenesis in von Hippel\u2010Lindau disease","volume":"63","author":"Vortmeyer AO","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493574"},{"key":"e_1_2_6_17_2","first-page":"1437","article-title":"Hereditary cancer, oncogenes, and antioncogenes","volume":"45","author":"Knudson AG","year":"1985","journal-title":"Cancer Res"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1960.17.4.0751"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.20090","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.20090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T13:00:02Z","timestamp":1697461202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.20090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,26]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,5]]}},"alternative-id":["10.1002\/ana.20090"],"URL":"https:\/\/doi.org\/10.1002\/ana.20090","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,4,26]]}}}