RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas
RNA Sequencing Provides Novel Insights into the Transcriptome of Aldosterone Producing Adenomas
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DOI：
10.1038/s41598-019-41525-2
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发表时间：
2019-04-18
影响因子：
4.6
通讯作者：
Bjorklund, Peyman
中科院分区：
文献类型：
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作者：
Backman, Samuel;Akerstrom, Tobias;Bjorklund, Peyman
原发性醛固酮增多症是继发性高血压的最常见形式，约30%的原发性醛固酮增多症患者的肾上腺中发生醛固酮腺瘤（APA）。KCNJ 5、ATP 1A 1、ATP 2B 3、CACNA 1D和CTNNB 1的体细胞突变在这些肿瘤中的比例接近60%。我们对15例醛固酮腺瘤（13例已知突变，2例无突变）进行了RNA测序和全基因组测序（n = 2）。在RNA-Seq读数中检测到所有已知的突变，并且在没有已知突变的肿瘤中发现了ATP 2B 3（G123 R）和CACNA 1D（S410 L）中的突变。CTNNB 1突变的腺瘤显示出大量差异表达的基因（1360个，而KCNJ 5和ATP 1A 1/ATP 2B 3分别为106和75个），并在分层聚类分析中聚集在一起。在49个APA的扩展队列中进行的RT-PCR证实了AFF 3和ISM 1在具有CTNNB 1突变的APA中的较高表达。对参与增殖和凋亡的基因表达的研究揭示了有和没有CTNNB 1突变的肿瘤之间的细微差异。总之，我们的研究结果巩固了CTNNB 1突变表征APA的不同亚组的概念。
Aldosterone producing adenomas (APAs) occur in the adrenal glands of around 30% of patients with primary aldosteronism, the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D and CTNNB1 have been described in similar to 60% of these tumours. We subjected 15 aldosterone producing adenomas (13 with known mutations and two without) to RNA Sequencing and Whole Genome Sequencing (n = 2). All known mutations were detected in the RNA-Seq reads, and mutations in ATP2B3 (G123R) and CACNA1D (S410L) were discovered in the tumours without known mutations. Adenomas with CTNNB1 mutations showed a large number of differentially expressed genes (1360 compared to 106 and 75 for KCNJ5 and ATP1A1/ATP2B3 respectively) and clustered together in a hierarchical clustering analysis. RT-PCR in an extended cohort of 49 APAs confirmed higher expression of AFF3 and ISM1 in APAs with CTNNB1 mutations. Investigation of the expression of genes involved in proliferation and apoptosis revealed subtle differences between tumours with and without CTNNB1 mutations. Together our results consolidate the notion that CTNNB1 mutations characterize a distinct subgroup of APAs.