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Endocrine Abstracts (2013) 32 S19.3 | DOI: 10.1530/endoabs.32.S19.3

Semmelweis University, Budapest, Hungary.

MicroRNA and mRNA expression patterns have been investigated in several studies on adrenocortical tumours and in some reports on phaeochromocytomas. These studies are relevant from pathogenic, diagnostic and therapeutic aspects. Under- and overexpressed microRNAs representing tumour suppressor and oncogenic microRNAs have been reported that can be helpful in the diagnosis for differentiating benign and malignant adrenocortical tumours (e.g. miR-503-miR-511, miR-195, miR-483-5p), recurrence-prone and non-recurring phaeochromocytomas (miR-1225-3p) and even benign and metastasing phaeochromocytoma (e.g. miR-15a, miR-16, miR-101, miR-183). Differentially expressed mRNAs and microRNAs have been identified that confer prognostic information. Based on mRNA expression patterns, adrenocortical cancer can be subdivided in two groups with different prognosis. Analysis of pathways affected by mRNAs and microRNAs has revealed several potentially druggable pathomechanisms e.g. mTor in adrenocortical tumours, Notch-signaling in phaeochromocytomas. Since the drug repertoire for treating adrenocortical cancer and malignant phaeochromocytoma is rather limited, these novel bioinformatics approaches might be of great relevance for deciphering novel pathways. By network analysis, we have found the underexpression of c-MYC in adrenocortical cancer that might be a central pathogenic event. Meta-analysis of adrenocortical tumour genomics data revealed three major pathomechanisms including: i) damage of cell cycle, ii) retinoic acid signalling via retinoid X receptor, iii) immune alterations. Based on these observations, our in vitro studies on 9-cis-retinoic acid in the adrenocortical cancer cell line NCI-H295R have shown the inhibition of growth and hormone secretion, and robust changes in gene expression patterns. 9-cis-retinoic acid also inhibited tumour growth in vivo in a xenograft model that might raise its potential applicability in the treatment of adrenocortical cancer. These findings may pave the way for novel diagnostic and even individualized treatment protocols.

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