{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:16:51Z","timestamp":1764688611025},"reference-count":15,"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>We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene(<jats:italic>Tsc2<\/jats:italic>), the gene predisposing to renal carcinoma(a) in the Eker rat. The homozygous mutant condition is lethal at around the 13th day of fetal life. In heterozygotes, RCs invariably develop in the first year of life. Histologically, RCs develop through multiple stages from early preneoplastic lesions(i.e., phenotypically altered tubules) to adenomas. The wild\u2010type allele mutation has been found even in the earliest preneoplastic lesions, fitting Knudson's two\u2010hit hypothesis and supporting the hypothesis that <jats:italic>Tsc2<\/jats:italic> is a tumor suppressor gene. In this study, homozygous deletion of the <jats:italic>Ink4<\/jats:italic> homologue on rat chromosome 5q was observed in 14 of 24(58%) RC\u2010derived cell lines. This may represent involvement of a second tumor suppressor gene, contributing to tumor progression. Considering previous results of studies of homozygous deletion of the <jats:italic>ifn\u03b1<\/jats:italic> gene in five of 24 cases(21%) and the <jats:italic>Ifn<\/jats:italic>\u03b2 gene in one of 24 cases(4%), the order of the genes may be <jats:italic>Ink4\u2013Ifna\u2014 Ifn\u03b2<\/jats:italic> Microsatellite instability was not observed in 26 Eker rat tumors.\u00a9 1995 Wiley\u2010Liss, Inc<\/jats:p>","DOI":"10.1002\/mc.2940140106","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T21:13:21Z","timestamp":1172092401000},"page":"23-27","source":"Crossref","is-referenced-by-count":23,"title":["Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis(<i>Tsc<\/i>2)"],"prefix":"10.1002","volume":"14","author":[{"given":"Okio","family":"Hino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etsuko","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youko","family":"Hirayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Tsuchiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,20]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/189858b0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.17.8038"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1993.tb02808.x"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.2324"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-70"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)37087-8"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.1.327"},{"key":"e_1_2_1_9_2","first-page":"2633","article-title":"Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat","volume":"54","author":"Kubo Y","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_1_10_2","first-page":"989","article-title":"Early detection of Knudson's two\u2010hits in the preneoplastic renal cells of the Eker rat model by the laser microdissection procedure","volume":"55","author":"Kubo Y","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910350103"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000133350"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(94)90307-7"},{"key":"e_1_2_1_14_2","first-page":"1529","article-title":"Eker rat model of dominantly inherited cancer syndrome","volume":"27","author":"Hino O","year":"1995","journal-title":"Transplant Proc"},{"key":"e_1_2_1_15_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_16_2","first-page":"6353","article-title":"Deletion of p16 and p15 genes in brain tumors","volume":"54","author":"Jen J","year":"1994","journal-title":"Cancer Res"}],"container-title":["Molecular 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