Genetics of adrenocortical tumors

Adrenocortical hyperplasia is a polyclonal process but ACTs are mostly monoclonal lesions [1-3], indicating that genetic changes at specific loci in the genome are needed for adrenal tumorigenesis. These include the genes coding for TP53, KIP2/p57, insulin-like growth factor type-II (IGF2), angiotensin-II, endothelin-1, diminuto/Dwarf-1, adrenomedullin, urotensin II, novH and cAMP-early repressor. Perhaps the best characterized gene so far is p53 (TP53). However, p53 expression does not always correlate with prognosis and it is rarely seen in monoclonal but highly differentiated tumors, indicating that mutations in this gene are a late event in the process of sporadic ACT formation [1,2,4]. In the present review, we will attempt to present a model of tumorigenesis for the adrenal cortex that stems from new data, collected over the last 10 years by molecular genomic, positional cloning and animal model approaches.