NO EVIDENCE FOR ONCOGENIC MUTATIONS IN THE ADRENOCORTICOTROPIN RECEPTOR GENE IN HUMAN ADRENOCORTICAL NEOPLASMS

The mechanism(s) of tumorigenesis for the majority of adrenocortical n eoplasms remain unknown. G-Protein-coupled receptors were recently pro posed as candidate protooncogenes. That activating mutations of this c lass of receptors might be important for tumor induction or progressio n of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine wh ether the ACTH receptor (ACTH-R) gene could be an oncogene in human ad renocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocor tical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cance r cell lines. We found no missense point mutations or even silent poly morphisms in any of the tumors and cell Lines studied. We conclude tha t activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis.