Germline and somatic genetic drivers of adrenocortical tumours

Adrenal tumours affect 1-4% of the population, with a prevalence increasing with age, tumours arising from the adrenal cortex being the most frequent, unlike the adrenomedullary tumours. Adrenocortical tumours are defined by their benign or malignant potential, and unilateral or bilateral, hormone-producing or non-functioning nature. As any tumoral formation, all adrenocortical tumours are clonal proliferations driven by genetic events, whether by a germline predisposition or by somatic alterations. By summarizing the genetic findings of the last 30 years of adrenocortical research, this review covers both the known germline causes of inherited bilateral nodular adrenocortical diseases, familial forms of hyperaldosteronism and adrenocortical carcinomas, and the somatic variants and copy-number variations found in sporadic adrenocortical adenomas and carcinomas, emphasizing on the signalling pathways involved. It also gives practical recommendations for genetic screening in routine clinical practice and clues for future research on the genetic basis of adrenocortical tumorigenesis.