{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T10:46:33Z","timestamp":1758969993848},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2625,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1997,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Individuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas. Tuberin, the protein product of the tuberous sclerosis complex\u20102 (<jats:italic>TSC2<\/jats:italic>) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes. To determine whether <jats:italic>TSC2<\/jats:italic> RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase\u2013polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas. Eighteen of 40 (45%) high\u2010grade (World Health Organization [WHO] grade III\/IV) astrocytomas and 4 of 8 (50%) adult low\u2010grade (WHO grade II) astrocytomas demonstrated reduced or absent <jats:italic>TSC2<\/jats:italic> expression, including 1 gaint cell astrocytoma, whereas none of the 10 pediatric low\u2010grade astrocytomas anlayzed showed a reduction in <jats:italic>TSC2<\/jats:italic> expression. Reduced or absent tuberin was observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the first time, that reduced or absent <jats:italic>TSC2<\/jats:italic> expression may represent one of the critical genetic events associated with the development of sporadic adult, but not pediatric, astrocytomas.<\/jats:p>","DOI":"10.1002\/ana.410420215","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:04:12Z","timestamp":1104591852000},"page":"230-235","source":"Crossref","is-referenced-by-count":32,"title":["Reduced <i>TSC2<\/i> RNA and protein in sporadic astrocytomas and ependymomas"],"prefix":"10.1002","volume":"42","author":[{"given":"Ralf","family":"Wienecke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhijit","family":"Guha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"John C.","family":"Maize","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard L.","family":"Heideman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"DeClue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Gutmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.10914"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_2_1_4_2","volume-title":"Tuberous sclerosis","author":"Gomez MR","year":"1988"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb37772.x"},{"key":"e_1_2_1_6_2","first-page":"764","article-title":"Localization of one gene for tuberous sclerosis within 9q32\u201034 and further evidence for heterogeneity","volume":"49","author":"Haines JL","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.16409"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0011"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90150-D"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90151-4"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90149-9"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90024-9"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.17.9154"},{"key":"e_1_2_1_15_2","first-page":"1477","article-title":"The tuberous sclerosis 2 gene is expressed at high levels in the adult cerebellum and developing spinal cord","volume":"6","author":"Geist RT","year":"1995","journal-title":"Cell Growth Differ"},{"key":"e_1_2_1_16_2","first-page":"913","article-title":"Co\u2010localization of the TSC2 product, tuberin, with its target Rap1 in the Golgi apparatus","volume":"13","author":"Wienecke R","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_1_17_2","first-page":"43","article-title":"Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues","volume":"150","author":"Wienecke R","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_1_18_2","doi-asserted-by":"crossref","unstructured":"KerfootC WieneckeR MenicheM et al. 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