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Transcriptome analysis of adrenocortical cancers: from molecular classification to the identification of new
Bruno Ragazzon1, Guillaume Assié, Jérôme Bertherat
1Institut Cochin, Université Paris Descartes, CNRS, UMR 8104, Inserm, U1016, Department of Endocrinology, Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014 Paris, France.
Abstract:
Transcriptome analysis has been successfully used to study the gene profile expression of adrenocortical tumors (ACT) for 7 years. The various studies reported to date have produced an abundance of new information on adrenocortical cancer (ACC), underlying the validity of this approach to study the molecular genetics and pathogenesis of these tumors. The gene expression profile of ACC clearly differs from that of benign adrenocortical adenomas (ACA). Interestingly, transcriptome analysis has the ability to establish a subclassification of ACC based on the gene expression profile. In particular, it is able to identify two groups of tumors with different outcomes (i.e. good prognosis and poor prognosis). This approach has been used to develop molecular markers for ACC diagnosis and prognostication. An IGF2 cluster of genes up-regulated in ACC has been identified. Transcriptome analysis has shown that, in comparison with ACA, IGF2 is indeed the gene most overexpressed in ACC. By contrast, genes associated with steroidogenesis are down-regulated in ACC. Genes controlling the cell cycle are dysregulated in ACC, and several are dramatically overexpressed. Analysis regarding the level of expression of Wnt/β-catenin and p53 signaling has shown alterations, in keeping with the known molecular somatic genetic defects of these pathways that are observed in ACC. This review summarizes the main findings of studies reporting ACC transcriptome analysis, demonstrating its power for ACT classification, and examines the resulting progress in understanding the pathogenesis of ACC. The potential for both ACC diagnosis and the identification of new therapeutic targets will be discussed.
Insights
Transcriptome analysis reveals distinct gene expression profiles in adrenocortical cancer (ACC) compared to benign adenomas (ACA). This approach aids in ACC subclassification, diagnosis, and identifying potential therapeutic targets.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Transcriptome analysis has been a key tool for studying adrenocortical tumors (ACT) for seven years.
- Previous studies highlight the utility of gene expression profiling in understanding adrenocortical cancer (ACC) molecular genetics and pathogenesis.
Purpose of the Study:
- To review findings from ACC transcriptome analyses.
- To demonstrate the power of transcriptome analysis for ACT classification.
- To examine progress in understanding ACC pathogenesis and identify diagnostic/therapeutic targets.
Main Methods:
- Gene expression profiling using transcriptome analysis.
- Comparison of gene expression patterns between ACC and benign adrenocortical adenomas (ACA).
- Analysis of signaling pathways including IGF2, steroidogenesis, cell cycle, Wnt/β-catenin, and p53.
Main Results:
- ACC exhibits a distinct gene expression profile compared to ACA.
- Transcriptome analysis can subclassify ACC into groups with different prognoses.
- IGF2 is significantly overexpressed in ACC, while steroidogenesis genes are down-regulated.
- Cell cycle genes are dysregulated, and Wnt/β-catenin and p53 pathways show alterations.
Conclusions:
- Transcriptome analysis is a powerful tool for classifying ACT and understanding ACC pathogenesis.
- This approach has led to the development of molecular markers for ACC diagnosis and prognostication.
- Further research holds potential for identifying new therapeutic targets for ACC.
