Multilayer‐omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome. Issue 6 (2nd May 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: International journal of cancer. Volume 135:Issue 6(2014:Sep. 15)
• Page Start: 1330
• Page End: 1342
• Publication Date: 2014-05-02
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28768
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>GCN1L1, MED12</italic> and <italic>CCNC</italic>, which are members of <italic>CDK8</italic> mediator complex directly regulating β‐catenin‐driven transcription, were identified in 16% of the RCCs. Mutations of <italic>MACF1</italic>, 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 <italic>ERC2</italic> and <italic>ABCA13</italic> were frequent in RCCs, and <italic>MTOR</italic> 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.</p> </abstract>