Genetics and epigenetics of adrenocortical tumors

Mol Cell Endocrinol. 2014 Apr 5;386(1-2):67-84. doi: 10.1016/j.mce.2013.10.028. Epub 2013 Nov 9.


Adrenocortical tumors are common neoplasms. Most are benign, nonfunctional and clinically irrelevant. However, adrenocortical carcinoma is a rare disease with a dismal prognosis and no effective treatment apart from surgical resection. The molecular genetics of adrenocortical tumors remain poorly understood. For decades, molecular studies relied on a small number of samples and were directed to candidate-genes. This approach, based on the elucidation of the genetics of rare genetic syndromes in which adrenocortical tumors are a manifestation, has led to the discovery of major dysfunctional molecular pathways in adrenocortical tumors, such as the IGF pathway, the Wnt pathway and TP53. However, with the advent of high-throughput methodologies and the organization of international consortiums to obtain a larger number of samples and high-quality clinical data, this paradigm is rapidly changing. In the last decade, genome-wide expression profile studies, microRNA profiling and methylation profiling allowed the identification of subgroups of tumors with distinct genetic markers, molecular pathways activation patterns and clinical behavior. As a consequence, molecular classification of tumors has proven to be superior to traditional histological and clinical methods in prognosis prediction. In addition, this knowledge has also allowed the proposal of molecular-targeted approaches to provide better treatment options for advanced disease. This review aims to summarize the most relevant data on the rapidly evolving field of genetics of adrenal disorders.

Keywords: Adenoma; Adrenocortical; Carcinoma; Epigenetics; Genetics; Hyperplasia.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex / pathology
  • Adrenal Cortex / physiopathology
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / pathology
  • Adrenal Cortex Neoplasms / physiopathology
  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Disease Models, Animal
  • Epigenesis, Genetic*
  • Humans
  • Signal Transduction / genetics