Abstract
Most adrenocortical tumors are benign, unilateral, adrenocortical adenomas that are often discovered incidentally. Adrenocortical cancer is rare. Exceptionally, adrenocortical tumors can be bilateral. Although most adrenocortical tumors occur sporadically, they may also feature in congenital and/or familial disease. The identification of germline genetic defects in familial diseases associated with adrenocortical tumors helped to define the somatic alterations in sporadic disease: for example, overexpression of insulin-like growth factor 2 and alterations at the 11p15 locus (observed in Beckwith–Wiedemann syndrome) are also found in most adrenocortical cancers. Similarly, inactivating mutations of the TP53 gene, located at 17p13 (observed in Li–Fraumeni syndrome), can also be found at the somatic level in sporadic adrenocortical cancers, as can 17p13 allelic losses. Components of the cyclic AMP signaling pathway—for example, adrenocorticotropic hormone receptors and other membrane receptors, Gs proteins and protein kinase A—can be altered to various degrees in adrenocortical tumors. More recently, gene profiling and genetic studies have shown that the Wnt–β-catenin signaling pathway is frequently activated in adrenocortical tumors. These research findings already have profound implications for clinical management of patients with adrenocortical tumors, for example in unraveling the genetic origin of the disease in some patients, and in the development of molecular markers for diagnosis and prognosis. The new findings should also help in the development of new therapeutic options.
Key Points
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The 17p13 (for TP53, tumor-suppressor p53) and 11p15 (for IGF2, insulin-like growth factor 2) loci are chromosomal regions that are involved in some rare forms of familial adrenocortical tumors
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17p13 and 11p15 are frequently altered in sporadic adrenocortical cancers
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Various components of the cyclic AMP signaling pathway (receptors, Gs proteins, protein kinase A) can be activated in benign, secreting, sporadic and/or familial adrenocortical tumors
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The Wnt–β-catenin signaling pathway can be activated in benign and malignant adrenocortical tumors
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Acknowledgements
This work was supported in part by the Plan Hospitalier de Recherche Clinique to the Adrenocortical and Medulla Endocrine Tumor (COMETE) network (AOM 02068), the Ligue National Contre le Cancer (Grant 04-7571), the Groupement d'Intérêt Scientifique–Institut National de la Santé et de la Recherche Médicale (GIS–INSERM) Institut des Maladies Rares for the Carney Complex network, and the European Network for the Study of Adrenal Tumors (ENSAT).
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Bertherat, J., Groussin, L. & Bertagna, X. Mechanisms of Disease: adrenocortical tumors—molecular advances and clinical perspectives. Nat Rev Endocrinol 2, 632–641 (2006). https://doi.org/10.1038/ncpendmet0321
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DOI: https://doi.org/10.1038/ncpendmet0321