Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.
Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.
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DOI：
10.1002/ijc.28768
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发表时间：
2014-09-15
影响因子：
6.4
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
--
作者：
Arai, Eri;Sakamoto, Hiromi;Ichikawa, Hitoshi;Totsuka, Hirohiko;Chiku, Suenori;Gotoh, Masahiro;Mori, Taisuke;Nakatani, Tamao;Ohnami, Sumiko;Nakagawa, Tohru;Fujimoto, Hiroyuki;Wang, Linghua;Aburatani, Hiroyuki;Yoshida, Teruhiko;Kanai, Yae
关键词：
本研究的目的是确定在肾癌发生过程中有显着影响的途径。使用Agilent SureSelect All Exon捕获对来自透明细胞肾细胞癌（RCC）患者的非癌性肾皮质组织和癌性组织两者的六十七个配对样品进行全外显子组、甲基化组和转录组分析，随后分别在Illumina HiSeq 2000平台、Illumina Infinium HumanMethylation 27 BeadArray和Agilent SurePrint Human Gene Expression微阵列上测序。进行桑格测序和定量逆转录PCR进行技术验证。使用MetaCore软件进行通路分析。共检测到2、153、359和8个基因的体细胞非同义单核苷酸突变、插入/缺失和基因内断裂。在16%的RCC中鉴定出GCN 1 L1、MED 12和CCNC的突变，这些突变是直接调节β-连环蛋白驱动的转录的CDK 8介体复合物的成员。在4%的RCC中鉴定出在Wnt/β-catenin信号通路中起作用的MACF 1突变。甲基化组和转录组分析的组合进一步强调了Wnt/β-连环蛋白信号通路在肾癌发生中的重要作用。肾癌中ERC 2和ABCA 13的基因畸变和表达降低是常见的，MTOR突变被认为是肾癌发生过程中细胞信号传导的主要干扰因素之一。我们的研究结果证实，多层组学分析可以是一个强大的工具，揭示在致癌作用中发挥重要作用的途径。
The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Illumina Infinium HumanMethylation27 BeadArray and Agilent SurePrint Human Gene Expression microarray, respectively. Sanger sequencing and quantitative reverse transcription-PCR were performed for technical verification. MetaCore software was used for pathway analysis. Somatic nonsynonymous single-nucleotide mutations, insertions/deletions and intragenic breaks of 2,153, 359 and 8 genes were detected, respectively. Mutations of GCN1L1, MED12 and CCNC, which are members of CDK8 mediator complex directly regulating β-catenin-driven transcription, were identified in 16% of the RCCs. Mutations of MACF1, which functions in the Wnt/β-catenin signaling pathway, were identified in 4% of the RCCs. A combination of methylome and transcriptome analyses further highlighted the significant role of the Wnt/β-catenin signaling pathway in renal carcinogenesis. Genetic aberrations and reduced expression of ERC2 and ABCA13 were frequent in RCCs, and MTOR mutations were identified as one of the major disrupters of cell signaling during renal carcinogenesis. Our results confirm that multilayer-omics analysis can be a powerful tool for revealing pathways that play a significant role in carcinogenesis.
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DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
影响因子：
3.9
作者：
Hicks, Stephanie;Wheeler, David A.;Plon, Sharon E.;Kimmel, Marek
通讯作者：
Kimmel, Marek
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1186/1756-9966-30-109
发表时间：
2011-11-22
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
He SB;Yuan Y;Wang L;Yu MJ;Zhu YB;Zhu XG
通讯作者：
Zhu XG
DOI：
10.1073/pnas.0709749105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Carrera, Ines;Janody, Florence;Treisman, Jessica E.
通讯作者：
Treisman, Jessica E.