Abstract:
: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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Satake N,Urakami S,Hirayama Y,Izumi K,Hino Odoi
10.1002/(sici)1097-0215(19980911)77:6<895::aid-ijcsubject
Has Abstractpub_date
1998-09-11 00:00:00pages
895-900issue
6eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19980911)77:6<895::AID-IJCjournal_volume
77pub_type
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