Institut 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.
Endocr Relat Cancer. 2011 Feb 23;18(2):R15-27. doi: 10.1530/ERC-10-0220. Print 2011 Apr.
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.
7 年来，转录组分析已成功用于研究肾上腺皮质肿瘤 (ACT) 的基因谱表达。迄今为止，各种已发表的研究报告为肾上腺皮质癌 (ACC) 提供了大量新信息，这证明了该方法在研究这些肿瘤的分子遗传学和发病机制方面的有效性。ACC 的基因表达谱明显不同于良性肾上腺皮质腺瘤 (ACA)。有趣的是，转录组分析有能力根据基因表达谱对 ACC 进行亚分类。特别是，它能够确定具有不同预后（即良好预后和不良预后）的两组肿瘤。这种方法已被用于开发 ACC 诊断和预后的分子标志物。已经鉴定出在 ACC 中上调的 IGF2 基因簇。转录组分析表明，与 ACA 相比，IGF2 确实是在 ACC 中过度表达的基因。相比之下，与类固醇生成相关的基因在 ACC 中下调。控制细胞周期的基因在 ACC 中失调，并且有几个基因显著过表达。关于 Wnt/β-catenin 和 p53 信号转导表达水平的分析显示了改变，与在 ACC 中观察到的这些通路的已知分子体细胞遗传缺陷一致。这篇综述总结了报告 ACC 转录组分析的研究的主要发现，证明了其对 ACT 分类的强大功能，并研究了 ACC 发病机制的理解方面取得的进展。将讨论 ACC 诊断和识别新治疗靶点的潜力。
