Single-CpG-resolution methylome analysis identifies clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas.
Single-CpG-resolution methylome analysis identifies clinicopathologically aggressive CpG island methylator phenotype clear cell renal cell carcinomas.
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DOI：
10.1093/carcin/bgs177
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发表时间：
2012-08
期刊：
影响因子：
4.7
通讯作者：
Kanai Y
中科院分区：
文献类型：
--
作者：
Arai E;Chiku S;Mori T;Gotoh M;Nakagawa T;Fujimoto H;Kanai Y
为了阐明DNA甲基化改变在肾癌发生过程中的意义，我们使用单cpg分辨率Infinium阵列对29个正常肾皮质组织(C)样本、107个非癌性肾皮质组织(N)样本和109个肿瘤组织(T)样本进行了甲基化分析。与C样品相比，N样品中4830个CpG位点的DNA甲基化水平已经改变。基于801个CpG位点DNA甲基化水平的无监督分层聚类分析，在N个样本中DNA甲基化改变发生，并在T个样本中遗传并加强，将透明细胞rcc聚为A类（N = 90）和B类（N = 14）。B类患者的无癌生存率和总生存率明显低于a类患者。B类透明细胞rcc以CpG岛DNA高甲基化积累为特征，被认为是CpG岛甲基化表型（CpG island methylator phenotype， CIMP）阳性癌症。FAM150A、GRM6、ZNF540、ZFP42、ZNF154、RIMS4、PCDHAC1、KHDRBS2、ASCL2、KCNQ1、PRAC、WNT3A、TRH、FAM78A、ZNF671、SLC13A5和NKX6-2基因上的CpG位点的DNA高甲基化成为rcc中CIMP的标志。另一方面，集群A的特征是全基因组DNA低甲基化。这些数据表明，癌前阶段DNA甲基化改变可能决定肿瘤的侵袭性和患者的预后。CpG岛上DNA超甲基化的积累和全基因组DNA低甲基化可能是肾癌发生的不同途径的基础。基于细菌人工染色体阵列的甲基化CpG岛扩增来自无原发性肾肿瘤患者的正常肾皮质组织CpG岛甲基化表型肝细胞癌透明细胞肾细胞癌患者的非癌性肾皮质组织
To clarify the significance of DNA methylation alterations during renal carcinogenesis, methylome analysis using single-CpG-resolution Infinium array was performed on 29 normal renal cortex tissue (C) samples, 107 non-cancerous renal cortex tissue (N) samples obtained from patients with clear cell renal cell carcinomas (RCCs) and 109 tumorous tissue (T) samples. DNA methylation levels at 4830 CpG sites were already altered in N samples compared with C samples. Unsupervised hierarchical clustering analysis based on DNA methylation levels at the 801 CpG sites, where DNA methylation alterations had occurred in N samples and were inherited by and strengthened in T samples, clustered clear cell RCCs into Cluster A (n = 90) and Cluster B (n = 14). Clinicopathologically aggressive tumors were accumulated in Cluster B, and the cancer-free and overall survival rates of patients in this cluster were significantly lower than those of patients in Cluster A. Clear cell RCCs in Cluster B were characterized by accumulation of DNA hypermethylation on CpG islands and considered to be CpG island methylator phenotype (CIMP)-positive cancers. DNA hypermethylation of the CpG sites on the FAM150A, GRM6, ZNF540, ZFP42, ZNF154, RIMS4, PCDHAC1, KHDRBS2, ASCL2, KCNQ1, PRAC, WNT3A, TRH, FAM78A, ZNF671, SLC13A5 and NKX6-2 genes became hallmarks of CIMP in RCCs. On the other hand, Cluster A was characterized by genome-wide DNA hypomethylation. These data indicated that DNA methylation alterations at precancerous stages may determine tumor aggressiveness and patient outcome. Accumulation of DNA hypermethylation on CpG islands and genome-wide DNA hypomethylation may each underlie distinct pathways of renal carcinogenesis. bacterial artificial chromosome array-based methylated CpG island amplification normal renal cortex tissue obtained from patients without any primary renal tumor CpG island methylator phenotype hepatocellular carcinoma non-cancerous renal cortex tissue obtained from patients with clear cell renal cell carcinomas National Center for Biotechnology Information renal cell carcinoma tumorous tissue Tumor-Node-Metastasis
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DOI：
10.1007/978-1-60327-367-1_5
发表时间：
2010-01-01
期刊：
GENETIC VARIATION: METHODS AND PROTOCOLS
影响因子：
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作者：
Barrett, Ian P.
通讯作者：
Barrett, Ian P.
影响因子：
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作者：
Gotoh M;Arai E;Wakai-Ushijima S;Hiraoka N;Kosuge T;Hosoda F;Shibata T;Kondo T;Yokoi S;Imoto I;Inazawa J;Kanai Y
通讯作者：
Kanai Y
影响因子：
3.8
作者：
Arai, Eri;Kanai, Yae
通讯作者：
Kanai, Yae
影响因子：
78.5
作者：
Issa, JP
通讯作者：
Issa, JP
影响因子：
64.8
作者：
通讯作者：
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