Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in chemically induced rat renal carcinoma cell

The Journal of Urology
S UrakamiO Hino

Abstract

von Hippel-Lindau (VHL) gene mutations are detected in noninherited, sporadic human renal cell carcinomas (RCs) at a high frequency. We recently identified a germline mutation in the rat homologue of the human tuberous sclerosis (TSC2) predisposing RC gene in the Eker rat model, and in this study we searched for mutations of the Tsc2 gene in chemically induced non-Eker rat RCs. Chemically [N-ethyl-N-hydroxyethylnitrosamine (EHEN)]-induced non-Eker rat RC lines (designated as BP13 and BP36B) were subjected to PCR-single strand conformation polymorphism (PCR-SSCP) analysis using specific primers covering entire exons of Tsc2 gene (41 coding exons and one non-coding exon). We simultaneously searched for mutations of Vhl gene, a rat homologue of von Hippel-Lindau disease gene (VHL) as well as Tsc2 gene. BP36B showed an abnormal mobility shift from the normal tissue of the same rat in exon 35 on analysis by PCR-SSCP. This mutation was confirmed by direct sequencing and found to be a T-to-C transition at the second position of codon 1470, resulting in an amino acid change from leucine to proline (missense mutation). This is the first demonstration of Tsc2 gene somatic mutation in non-Eker rat RCs. Our present findings call attention ...Continue Reading

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Citations

Oct 3, 2002·Cancer Letters·Yih-Horng ShiaoDouglas C Wolf
Apr 24, 2003·Cancer Science·Okio HinoKazuo Okimoto
Nov 28, 2000·Japanese Journal of Cancer Research : Gann·K OkimotoO Hino
Oct 18, 2016·Pediatric Blood & Cancer·Samara L PotterD Williams Parsons
Oct 31, 2003·Molecular Carcinogenesis·Sonal K PatelSerrine S Lau
Apr 19, 2018·The American Journal of Surgical Pathology·Megan ParillaTatjana Antic
Aug 26, 1998·International Journal of Cancer. Journal International Du Cancer·N SatakeO Hino
May 12, 2000·American Journal of Physiology. Renal Physiology·V MurthyV Ramesh
Jul 12, 2002·American Journal of Physiology. Renal Physiology·Hae-Seong YoonSerrine S Lau
Jan 28, 2003·The American Journal of Pathology·Shengli CaiCheryl Lyn Walker

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