Pathogenesis of adrenocortical cancer

The study of the clonality of adrenocortical tumours (ACTs) has shown that adrenocortical cancers (ACCs) are of monoclonal origin. Numerous chromosomal alterations have been observed in ACCs, and they are much more frequent than in adrenocortical adenomas. Progress in the genetics of familial syndromes associated with ACTs helped to identify significant somatic molecular alterations in sporadic adult ACCs. Somatic mutations of the tumour suppressor gene TP53 are observed in a third of ACCs. Interestingly, allelic losses (LOH) at the TP53 locus (17p13) are very frequent, observed in more than 85% of ACCs. The insulin-like growth factor II (IGF-II) locus (11p15) is imprinted. IGF-II is over-expressed in 90% of ACCs. Transcriptome studies have identified an IGF-II cluster of genes significantly over-expressed in ACCs. Transcriptome analysis suggests also that the Wnt/β-catenin signalling pathway is activated in ACT. About a third of ACCs harbours somatic activating mutations of the β-catenin gene. This recent progress in the molecular genetics of ACC has led to the development of new molecular markers for the diagnosis of malignancy; these might also help to identify prognostic markers of ACC and may ultimately lead to novel therapeutic approaches.

Keywords: adrenocortical cancer, IGF-II, TP53, β-catenin, trancriptome