Mutation analysis of the NR5A1 and P53 tumor suppressor gene of normal adrenals and cortisol-secreting adrenocortical tumors in dogs

Abstract

The steroidogenic factor 1 (SF-1) plays an important role in adrenal development in humans and mice and there are also indications that the regulation of the SF-1 protein level is critical for the cortisol-secreting adrenocortical tumor (AT) development. The NR5A1 gene encodes for SF-1. Also the P53 tumor suppressor gene plays a role in the development of childhood ATs. In this study we searched for activating mutations in the P53 tumor suppressor gene and the NR5A1 gene. No activating mutations were detected in the NR5A1 gene, only 3 silent mutations in the NR5A1 gene of 3 carcinomas. In the P53 tumor suppressor gene one activating mutation was detected in a carcinoma and one silent mutation in an adenoma. The results of this study suggests that the activation of SF-1 in canine ATs is not a result of mutation and that P53 mutations also do not play an important role.