{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:42:03Z","timestamp":1786977723690,"version":"build-2736575974"},"reference-count":75,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T00:00:00Z","timestamp":1097539200000},"content-version":"vor","delay-in-days":3268,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[1995,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Most of the genes for hereditary tumor syndromes cloned thus far have subsequently been shown to be mutated not only in the germlines and tumors from patients with the relatively rare inherited disease, but also in the much more common sporadic tumor counterparts in the general population. Thus, the isolation and functional characterization of genes associated with hereditary tumor syndromes have emerged as a major strategy to gain insights into some of the most fundamental mechanisms of tumorigenesis.<\/jats:p>\n                  <jats:p>The search for the genes causing two hereditary tumor syndromes of the nervous system, neurofibromatosis type 2 (NF2) and von Hippel\u2010Lindau disease (VHL), has recently culminated in the cloning of both disease genes. This represents another successful application of the so\u2010called positional cloning approach, i.e., the isolation of a hereditary disease gene with unknown function, based on the determination of its chromosomal location in the human genome.<\/jats:p>\n                  <jats:p>\n                    The gene for NF2, a syndrome typically associated with vestibular schwannomas and meningiomas, is homologous with a family of genes whose members appear to play an important role in bridging the cell membrane with the intracellular cytoskeleton, including moesin, ezrin, radixin, and protein 4.1. Recent mutation analyses have revealed that the\n                    <jats:italic>NF2<\/jats:italic>\n                    tumor suppressor gene is frequently mutated not only in vestibular schwannomas and meningiomas from NF2 patients, but also in their sporadic counterparts, which represent approximately one\u2010third of all human brain tumors. Furthermore, malignant human tumors seemingly unrelated to the NF2 syndrome, such as neural crest\u2010derived malignant melanomas, as well as malignant mesotheliomas (a pleural mesoderm\u2010derived tumor), have also been found to be frequently mutated or deleted in the\n                    <jats:italic>NF2<\/jats:italic>\n                    locus, suggesting a broader role for the\n                    <jats:italic>NF2<\/jats:italic>\n                    gene in the initiation and progression of human neoplasms.\n                  <\/jats:p>\n                  <jats:p>\n                    VHL is a rare tumor syndrome characterized by certain types of nervous system tumors (cerebellar and spinal hemangioblastomas as well as retinal angiomas), in conjunction with bilateral renal cell carcinomas and pheochromocytomas. Similar to NF2, recent genetic mutation studies have revealed that the\n                    <jats:italic>VHL<\/jats:italic>\n                    tumor suppressor gene is not only mutated in the hereditary tumors from VHL patients, but also in their sporadic counterparts. Importantly, the\n                    <jats:italic>VHL<\/jats:italic>\n                    gene represents the most frequently mutated cancer\u2010related gene thus far identified in sporadic renal cell carcinoma. In contrast to most other hereditary cancer syndromes, however,\n                    <jats:italic>VHL<\/jats:italic>\n                    mutations are surprisingly specific for tumors typically associated with the VHL syndrome, and have not been detected in any other tumor type unrelated to VHL.\n                  <\/jats:p>\n                  <jats:p>\n                    The cloning and initial genetic characterization of the\n                    <jats:italic>NF2<\/jats:italic>\n                    and\n                    <jats:italic>VHL<\/jats:italic>\n                    genes have now provided a rational basis for subsequent functional studies on the elucidation of the normal and tumor\u2010associated cellular signaling pathways of these tumor suppressor genes. \u00a9 1995 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/glia.440150310","type":"journal-article","created":{"date-parts":[[2005,5,12]],"date-time":"2005-05-12T14:23:50Z","timestamp":1115907830000},"page":"297-307","source":"Crossref","is-referenced-by-count":15,"title":["Neurofibromatosis type 2 and von Hippel\u2010Lindau disease: From gene cloning to function"],"prefix":"10.1002","volume":"15","author":[{"given":"Nikolai","family":"Kley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Whaley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd R.","family":"Seizinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.120.1.129"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.4.565"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3107130"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0294-185"},{"key":"e_1_2_1_6_1","unstructured":"Bianchi A. 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