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Biallelic mutations of the Tsc2 gene in chemically induced rat renal cell carcinoma
Author(s) -
Satake Nobuo,
Urakami Shinji,
Hirayama Youko,
Izumi Keisuke,
Hino Okio
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980911)77:6<895::aid-ijc16>3.0.co;2-0
Subject(s) - tsc2 , exon , gene , biology , coding region , microbiology and biotechnology , germline mutation , mutation , single strand conformation polymorphism , cancer research , tuberous sclerosis , genetics , pathology , medicine , apoptosis , pi3k/akt/mtor pathway
A number of cancer genes have been identified by the study of hereditary human cancers and shown to be involved in sporadic genesis of the same tumors. We have identified a germline mutation in the rat homologue of the human tuberous sclerosis ( TSC2 ) predisposing gene in the Eker rat model. In this study, we searched for mutations of the Tsc2 gene in chemically induced non‐Eker rat renal cell carcinomas (RCs). N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN)‐ and diethylnitrosamine (DEN)‐induced non‐Eker rat primary RCs were subjected to polymerase chain reaction‐single strand conformational polymorphism (PCR‐SSCP) analysis using specific primers covering all exons of the Tsc2 gene (41 coding exons and 1 non‐coding exon). We simultaneously searched for mutations in the Vhl gene, a rat homologue of von Hippel‐Lindau disease ( VHL ) gene, as well as the Tsc2 gene. Mutations in the Vhl gene were not detected in any rat RCs (0/8). In contrast, Tsc2 gene mutations were detected at a high frequency in EHEN‐induced RCs (2/3) and DEN‐induced RCs (3/5) (total 5/8) ( p < 0.05). By a direct cloning approach utilizing PCR analysis in 2 applicable cases, we could demonstrate the presence of intragenic somatic mutations in both alleles of the Tsc2 gene. Our results suggest that Tsc2 gene inactivation plays an important role in EHEN‐ and DEN‐induced RCs as well as in Eker rat RCs. Int. J. Cancer 77:895–900, 1998.© 1998 Wiley‐Liss, Inc.