DNA methylation analysis in malignant pheochromocytoma and paraganglioma.
DNA methylation analysis in malignant pheochromocytoma and paraganglioma.
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DOI：
10.1016/j.jcte.2016.12.004
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发表时间：
2017-03
影响因子：
3
通讯作者：
Oki Y
中科院分区：
文献类型：
--
作者：
Oishi T;Iino K;Okawa Y;Kakizawa K;Matsunari S;Yamashita M;Taniguchi T;Maekawa M;Suda T;Oki Y
我们试图建立PCC/PGLs恶性转化的表观遗传学。采用全基因组甲基化分析检测良性和恶性PCC/PGLs。通过分析单个基因组区域来缩小选择的候选CpG。剩下两个作为最终候选者，分别与ACSBG 1和MAST 1相关。这些基因的表观遗传学可能参与了PCC/PGL的恶性转化。近年来，在多种恶性肿瘤中发现了特定CpG位点的异常甲基化，启动子CpG位点的表观遗传调控被认为是肿瘤发生的重要机制。本研究旨在通过甲基化分析建立恶性嗜铬细胞瘤（PCC）和副神经节瘤（PGL）恶变的表观遗传学。基于Infinium HumanMethylation 450 BeadChip阵列使用PCC/PGL患者的DNA样品的结果，选择在转移性肿瘤中相对于2名恶性PCC/PGL患者的原发性肿瘤中的那些高/低甲基化的候选CpG位点。定量评价所选候选CpG位点的甲基化水平。选择12个CpG位点作为高甲基化候选物，并且选择16个CpG位点作为低甲基化候选物。使用两种定量甲基化分析方法，一个高甲基化位点（cg 02119938）和一个低甲基化位点（cg 26870725）仍然是候选者。这些位点分别与ACSBG 1（酰基辅酶A合成酶泡泡糖家族成员1）和MAST 1（微管相关丝氨酸-苏氨酸激酶1）相关。ACSBG 1和MAST 1的免疫组化研究表明，在PCC/PGL恶性转化的表观遗传学变化可能与ACSBG 1沉默或MAST 1过表达。在这里，我们报告了两个值得注意的基因，ACSBG 1和MAST 1;这些基因的异常启动子甲基化/去甲基化可能参与了它们在恶性PCC/PGL中的沉默/表达。进一步的研究是必要的，以确定ACSBG 1和/或MAST 1的表达在恶性转化中的作用，并建立病理标志物，可以评估PCC/PGL的恶性潜力。
We tried to establish the epigenetics of malignant transformation in PCC/PGLs. Benign and malignant PCC/PGLs were examined using whole genomic methylation analysis. Selected candidate CpGs were narrowed down by analysis of individual genomic regions. Two were left as the final candidates, related to ACSBG1 and MAST1 respectively. Epigenetics in these genes might be involved in malignant transformation of PCC/PGLs. In recent years, aberrant DNA methylation of specific CpG sites has been detected in many types of malignant tumors, and the epigenetic regulation of promoter CpG sites is considered an important mechanism underlying carcinogenesis. This study aimed to establish the epigenetics of the malignant transformation of malignant pheochromocytoma (PCC) and paraganglioma (PGL) by performing a methylation analysis. Based on the results of the Infinium HumanMethylation450 BeadChip array using DNA samples of PCC/PGL patients, candidate CpG sites that were hyper/hypo-methylated in metastatic tumors relative to those in the primary tumors of 2 patients with malignant PCC/PGL were selected. The methylation levels of the chosen candidate CpG sites were evaluated quantitatively. Twelve CpG sites were selected as hypermethylated candidates, and 16 CpG sites were selected as hypomethylated candidates. Using two quantitative methylation analysis methods, one hypermethylated site (cg02119938) and one hypomethylated site (cg26870725) remained as candidates. These sites were related to ACSBG1 (acyl-CoA synthetase bubblegum family member 1) and MAST1 (microtubule-associated serine-threonine kinase 1), respectively. Immunohistochemical studies of ACSBG1 and MAST1 revealed that epigenetic changes in the malignant transformation of PCC/PGL might be associated with ACSBG1 silencing or MAST1 overexpression. Here, we report two noteworthy genes, ACSBG1 and MAST1; the aberrant promoter methylation/demethylation of these genes might be involved in their silencing/expression in malignant PCC/PGL. Further investigations are necessary to determine the role of ACSBG1 and/or MAST1 expression in malignant transformation and to establish pathological markers that can evaluate the malignant potential of PCC/PGL.