Abstract
We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene(Tsc2), 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 wildβtype allele mutation has been found even in the earliest preneoplastic lesions, fitting Knudson's twoβhit hypothesis and supporting the hypothesis that Tsc2 is a tumor suppressor gene. In this study, homozygous deletion of the Ink4 homologue on rat chromosome 5q was observed in 14 of 24(58%) RCβderived 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 ifnΞ± gene in five of 24 cases(21%) and the __Ifn__Ξ² gene in one of 24 cases(4%), the order of the genes may be Ink4βIfnaβ IfnΞ² Microsatellite instability was not observed in 26 Eker rat tumors.Β© 1995 WileyβLiss, Inc