We have recently identified on rat chromosome 10q a germline mutation in the 
tuberous sclerosis gene (Tsc2), the gene predisposing to renal carcinoma (RC) 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-type allele mutation has been found even in the earliest preneoplastic 
lesions, fitting Knudson's two-hit 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%) RC-derived 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 Ifn alpha gene in five of 24 cases (21%) and the Ifn 
beta gene in one of 24 cases (4%), the order of the genes may be Ink4-Ifn 
alpha-Ifn beta. Microsatellite instability was not observed in 26 Eker rat 
tumors.