“Second hit” of Tsc2 gene in radiation induced renal tumors of Eker rat model

Abstract

Cancer is a heritable disorder of the somatic cells. The environment and heredity both operate in the origin of human cancer. Hereditary cancers should prove valuable in elucidating carcinogenesis. The Eker rat model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. We, along with others, identified a germline mutation in the rat homologus of the human tuberous sclerosis gene ( TSC2) as the predisposing Eker gene. We previously reported that a qualitative difference in the second hit of the Tsc2 gene exists between spontaneous and ENU-induced mutations (e.g., deletion or duplication versus point mutation). In this study, we show the second hit of the Tsc2 gene in radiation-induced RCs.