Genetics and epigenetics of adrenocortical tumors.
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.
Adrenal Disorders Unit - LIM/42, Department of Endocrinology and Metabolism, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, Brazil.
Antonio M
AM
Lerario
Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine Endocrine Oncology Program, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5902, USA.
Andreas
A
Moraitis
Endocrine Oncology Program, Center for Organogenesis, University of Michigan Health System, 109 Zina Pitcher Place, 1528 BSRB, Ann Arbor, MI 48109-2200, USA. Electronic address: ghammer@med.umich.edu.
Gary D
GD
Hammer
D000302:Adrenal Cortex / Q000473:pathology / Q000503:physiopathology; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D015398:Signal Transduction / Q000235:genetics
Adenoma; Adrenocortical; Carcinoma; Epigenetics; Genetics; Hyperplasia