Analysis of DNA methylation patterns associated with the gastric cancer genome

被引:35
作者
Cheng, Yi [1 ,2 ]
Yan, Zhi [2 ]
Liu, Yin [1 ]
Liang, Chengbai [1 ]
Xia, Hong [1 ]
Feng, Junming [3 ]
Zheng, Guorong [2 ]
Luo, Hesheng [1 ]
机构
[1] Wuhan Univ, Remin Hosp, Dept Gastroenterol, Wuhan 430060, Hubei, Peoples R China
[2] Wuhan Gen Hosp Guangzhou Command, Dept Gastroenterol, Wuhan 430070, Hubei, Peoples R China
[3] Wuhan Gen Hosp Guangzhou Command, Dept Pathol, Wuhan 430070, Hubei, Peoples R China
关键词
methylation microarray; genome-wide; gastric cancer; DNA methylation;
D O I
10.3892/ol.2014.1838
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The objective of the current study was to investigate the characteristics of DNA methylation patterns associated with the gastric cancer genome and to identify clinically useful diagnostic markers and therapeutic targets for gastric cancer. The Infinium 450K methylation microarray was used to compare differential DNA methylation sites of gastric cancer tissue with that of normal gastric tissue. The results of the DNA microarray analysis were confirmed by pyrosequencing. Functional analysis of the differential genes was performed using the GO software. The effect of candidate site methylation on gene expression was monitored using quantitative polymerase chain reaction analysis. Of the 2,645 differential methylation sites identified in gastric cancer tissues, 2,016 were hypermethylated sites, 629 were hypomethylated sites, 826 were located in promoter regions and 1,024 were located within genes. These differential sites were associated with 1,352 genes. In total, five sites were selected and pyrosequencing verified the results of the microarray analysis in five of the sites. Change in gastric cancer DNA methylation pattern was a common occurrence. Differential methylation sites appeared more often in non-promoter regions. The associated genes were involved in multiple signaling pathways, and hypermethylated and hypomethylated sites were involved in roughly the same signaling pathways. Methylation of the genome promoted gene expression. TRIM15, ITGAM, MSX2 and FAM38A may be candidate genes for diagnosing gastric cancer.
引用
收藏
页码:1021 / 1026
页数:6
相关论文
共 13 条
[1]
Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells [J].
Ball, Madeleine P. ;
Li, Jin Billy ;
Gao, Yuan ;
Lee, Je-Hyuk ;
LeProust, Emily M. ;
Park, In-Hyun ;
Xie, Bin ;
Daley, George Q. ;
Church, George M. .
NATURE BIOTECHNOLOGY, 2009, 27 (04) :361-368
[2]
Brenner Hermann, 2009, V472, P467, DOI 10.1007/978-1-60327-492-0_23
[3]
Dedeurwaerder S, 2011, EPIGENOMICS-UK, V3, P771, DOI [10.2217/epi.11.105, 10.2217/EPI.11.105]
[4]
On the presence and role of human gene-body DNA methylation [J].
Jjingo, Daudi ;
Conley, Andrew B. ;
Yi, Soojin V. ;
Lunyak, Victoria V. ;
Jordan, I. King .
ONCOTARGET, 2012, 3 (04) :462-474
[5]
Studying the epigenome using next generation sequencing [J].
Ku, Chee Seng ;
Naidoo, Nasheen ;
Wu, Mengchu ;
Soong, Richie .
JOURNAL OF MEDICAL GENETICS, 2011, 48 (11) :721-730
[6]
Principles and challenges of genome-wide DNA methylation analysis [J].
Laird, Peter W. .
NATURE REVIEWS GENETICS, 2010, 11 (03) :191-203
[7]
Screening for gastric cancer in Asia: current evidence and practice [J].
Leung, Wai K. ;
Wu, Ming-shiang ;
Kakugawa, Yasuo ;
Kim, Jae J. ;
Yeoh, Khay-guan ;
Goh, Khean Lee ;
Wu, Kai-chun ;
Wu, Deng-chyang ;
Sollano, Jose ;
Kachintorn, Udorn ;
Gotodo, Takuji ;
Lin, Jaw-town ;
You, Wei-cheng ;
Ng, Enders K. W. ;
Sung, Joseph J. Y. .
LANCET ONCOLOGY, 2008, 9 (03) :279-287
[8]
Human DNA methylomes at base resolution show widespread epigenomic differences [J].
Lister, Ryan ;
Pelizzola, Mattia ;
Dowen, Robert H. ;
Hawkins, R. David ;
Hon, Gary ;
Tonti-Filippini, Julian ;
Nery, Joseph R. ;
Lee, Leonard ;
Ye, Zhen ;
Ngo, Que-Minh ;
Edsall, Lee ;
Antosiewicz-Bourget, Jessica ;
Stewart, Ron ;
Ruotti, Victor ;
Millar, A. Harvey ;
Thomson, James A. ;
Ren, Bing ;
Ecker, Joseph R. .
NATURE, 2009, 462 (7271) :315-322
[9]
Conserved role of intragenic DNA methylation in regulating alternative promoters [J].
Maunakea, Alika K. ;
Nagarajan, Raman P. ;
Bilenky, Mikhail ;
Ballinger, Tracy J. ;
D'Souza, Cletus ;
Fouse, Shaun D. ;
Johnson, Brett E. ;
Hong, Chibo ;
Nielsen, Cydney ;
Zhao, Yongjun ;
Turecki, Gustavo ;
Delaney, Allen ;
Varhol, Richard ;
Thiessen, Nina ;
Shchors, Ksenya ;
Heine, Vivi M. ;
Rowitch, David H. ;
Xing, Xiaoyun ;
Fiore, Chris ;
Schillebeeckx, Maximiliaan ;
Jones, Steven J. M. ;
Haussler, David ;
Marra, Marco A. ;
Hirst, Martin ;
Wang, Ting ;
Costello, Joseph F. .
NATURE, 2010, 466 (7303) :253-U131
[10]
Epigenome-wide association studies for common human diseases [J].
Rakyan, Vardhman K. ;
Down, Thomas A. ;
Balding, David J. ;
Beck, Stephan .
NATURE REVIEWS GENETICS, 2011, 12 (08) :529-541