There is a variety of adrenocortical tumors that can be responsible for different cortisol excess levels. Genomics allowed recently many progress in this field. Exome sequencing allowed to identify somatic activating mutations of the catalytic subunit of PKA (PRKACA) in cortisol secreting adenomas responsible for overt-Cushing. Combining pangenomic snp analysis and whole genome sequencing led to the identification of inactivating germline mutations of a new tumor suppressor gene, ARMC5, in primary bilateral macronodular adrenal hyperplasia. The use of genomics in adrenocortical cancer give now a clear description of the mRNA and miRNA expression profile (transcriptome), as well as chromosomal and methylation alterations. Exome sequencing combined with pangenomic snp analysis revealed alterations of key driver genes in adrenocortical cancer, like CTNNB1, TP53, CDKN2A, DAXX, TERT, MEN1, RB1… It also revealed that the most frequently altered gene is ZNRF3, a new tumor suppressor gene identified by this approach, and likely to control the Wnt/β-catenin pathway. Interestingly, genomics study of adrenocortical cancer also revealed subtype of malignant tumors with different pattern of molecular alterations associated with different outcome.
Clearly genomics studies led to a new vision of adrenocortical tumors classification based on molecular analysis. This open new perspectives not only to unravel the adrenal tumorigenesis but also for the development of various molecular tools to classify adrenocortical tumors and guide patient management for a precision medicine.
17 - 19 Feb 2016
European Society of Endocrinology