PMID: 7546221Sep 1, 1995Paper

Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (Tsc2)

Molecular Carcinogenesis
Okio HinoH Mitani

Abstract

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.

References

Dec 1, 1992·The Journal of Urology·J I EverittC L Walker
Aug 15, 1994·Cancer Letters·O HinoY Kubo
Sep 15, 1994·Biochemical and Biophysical Research Communications·O HinoY Hirayama
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·R S YeungA G Knudson
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Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·O HinoA G Knudson

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Citations

Jan 1, 1995·Journal of Cancer Research and Clinical Oncology·O HinoK Orimoto
Nov 21, 1998·Biochimica Et Biophysica Acta·M Ruas, G Peters
Oct 7, 1998·Epilepsy Research·H V VintersJ E DeClue
Aug 5, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jennifer D CohenSerrine S Lau
Jun 25, 2004·Radiology·Francesco G GaraciGiovanni Simonetti
Feb 21, 2006·The European Journal of Neuroscience·Christian von der BrelieTimo Kirschstein
Apr 30, 1999·Gastroenterology·R J GuanA B Pardee
Apr 24, 2003·Cancer Science·Okio HinoKazuo Okimoto
Feb 15, 2001·Chemical Research in Toxicology·S S LauC L Walker

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