{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:36:15Z","timestamp":1760297775077},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":3975,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[1995,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Somatic events leading to the inactivation of tumor suppressor genes often involve chromosomal alterations that can be detected as loss of heterozygosity(a). In the Eker rat, spontaneous tumors of the kidney, uterus, and spleen develop as a result of a germline mutation of the tuberous sclerosis 2(<jats:italic>Tsc2<\/jats:italic>) gene. We examined the pattern and frequency of LOH at the predisposing locus in 77 primary tumors and cell lines to gain an understanding of the role of <jats:italic>Tsc2<\/jats:italic> allelic loss in the pathogenesis of Eker\u2010derived tumors. Although most renal and uterine tumors(primary and cell lines) displayed LOH, splenic hemangiosarcomas did not. Although the presence of normal tissue may account for some of this difference, the possibility exists that an alternative mechanism, such as subtle mutation or gene dosage effects, may be involved during splenic tumorigenesis. Northern analysis confirmed that LOH resulted in loss of the wild\u2010type transcripts for the <jats:italic>Tsc2<\/jats:italic> gene. Thus, the inactivation of both alleles plays an important role in renal and uterine tumor development, in keeping with Knudson's two\u2010hit hypothesis. In addition, renal tumors that retained the wild\u2010type allele also did not express the normal transcript, suggesting that the remaining <jats:italic>Tsc2<\/jats:italic>alleles had acquired subtle mutations resulting in loss of gene function.\u00a9 1995 Wiley\u2010Liss, Inc<\/jats:p>","DOI":"10.1002\/mc.2940140107","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T21:13:21Z","timestamp":1172092401000},"page":"28-36","source":"Crossref","is-referenced-by-count":51,"title":["Allelic loss at the tuberous sclerosis 2 locus in spontaneous tumors in the Eker rat"],"prefix":"10.1002","volume":"14","author":[{"given":"Raymond S.","family":"Yeung","sequence":"first","affiliation":[]},{"given":"Guang\u2010Hui","family":"Xiao","sequence":"additional","affiliation":[]},{"given":"Jeffery I.","family":"Everitt","sequence":"additional","affiliation":[]},{"given":"Fang","family":"Jin","sequence":"additional","affiliation":[]},{"given":"Cheryl L","family":"Walker","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,7,20]]},"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":"10.1111\/j.1699-0463.1954.tb00301.x"},{"key":"e_1_2_1_4_2","first-page":"99","article-title":"Hereditary renal adenomas and adenocarcinomas in rats","volume":"4","author":"Eker R","year":"1981","journal-title":"Diagnostic Histopathology"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)37087-8"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.1.327"},{"key":"e_1_2_1_7_2","unstructured":"EverittJL WolfDC HoweSR GoldsworthyTL WalkerC. Rodent model of reproductive tract leiomyomata: Clinical and pathologic features.Am J Pathol in press."},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1553556"},{"key":"e_1_2_1_9_2","first-page":"5856","article-title":"Genetic predisposition to transplacentally induced renal cell carcinomas in the Eker rat","volume":"53","author":"Hino O","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.24.11413"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-70"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_1_13_2","unstructured":"HoweSR GohardisMM EverittJL GoldsworthyTL WolfDC WalkerC. Rodent model of reproductive tract leiomyomata: Establishment and characterization of tumor\u2010derived cell lines.Am J Pathol in press."},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.8038"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"e_1_2_1_16_2","first-page":"289","volume-title":"Comparative Molecular Carcinogenesis","author":"Walker C","year":"1992"},{"key":"e_1_2_1_17_2","first-page":"2973","article-title":"Altered expression of transforming growth factor\u2010a in hereditary rat renal cell carcinoma","volume":"51","author":"Walker C","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940040504"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940120408"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0294-193"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.10.1833"},{"key":"e_1_2_1_22_2","first-page":"2728","article-title":"Association between wild type and mutant APC gene products","volume":"53","author":"Su L\u2010K","year":"1993","journal-title":"Cancer Res"},{"key":"e_1_2_1_23_2","first-page":"5","article-title":"Human haploinsufficiency\u2014one for sorrow, two for joy","volume":"7","author":"Fisher E","year":"1994","journal-title":"Genet"},{"key":"e_1_2_1_24_2","first-page":"1057","article-title":"Quantitative effects of the retinoblastoma gene on mouse development and tissue\u2010specific tumorigenesis","volume":"4","author":"Chang C\u2010Y","year":"1993","journal-title":"Cell Growth Differ"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90194-4"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.2940140107","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.2940140107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T05:05:30Z","timestamp":1698296730000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.2940140107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,9]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,9]]}},"alternative-id":["10.1002\/mc.2940140107"],"URL":"https:\/\/doi.org\/10.1002\/mc.2940140107","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,9]]}}}