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Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer.

Authors
 Sunwoo Lee ; Taejeong Oh ; SungWhan An ; Miae Yoo ; Chanhee Park ; Namkyu Kim ; Seunghoon Lee ; Dongjun Jeong ; Benjamin D. Hoehn ; Youngho Moon ; Changjin Kim ; Sunyoung Rha ; Hyuncheol Chung 
Citation
 International Journal of Oncology, Vol.40(3) : 889~898, 2012 
Journal Title
 International Journal of Oncology 
ISSN
 1019-6439 
Issue Date
2012
Abstract
Aberrant methylation of CpG islands in the promoter region of genes is a common epigenetic phenomenon found in early cancers. Therefore conducting genome-scale methylation studies will enhance our understanding of the epigenetic etiology behind carcinogenesis by providing reliable biomarkers for early detection of cancer. To discover novel hypermethylated genes in colorectal cancer by genome-wide search, we first defined a subset of genes epigenetically reactivated in colon cancer cells after treatment with a demethylating agent. Next, we identified another subset of genes with relatively down-regulated expression patterns in colorectal primary tumors when compared with normal appearing-adjacent regions. Among 29 genes obtained by cross-comparison of the two gene-sets, we subsequently selected, through stepwise subtraction processes, two novel genes, GABRA1 and LAMA2, as methylation targets in colorectal cancer. For clinical validation pyrosequencing was used to assess methylation in 134 matched tissue samples from CRC patients. Aberrant methylation at target CpG sites in GABRA1 and LAMA2 was observed with high frequency in tumor tissues (92.5% and 80.6%, respectively), while less frequently in matched tumor-adjacent normal tissues (33.6% for GABRA1 and 13.4% for LAMA2). Methylation levels in primary tumors were not significantly correlated with clinico-pathological features including age, sex, survival and TNM stage. Additionally, we found that ectopic overexpression of GABRA1 in colon cancer cell lines resulted in strong inhibition of cell growth. These results suggest that two novel hypermethylated genes in colorectal cancer, GABRA1 and LAMA2, may have roles in colorectal tumorigenesis and could be potential biomarkers for the screening and the detection of colorectal cancer in clinical practice.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90502
DOI
10.3892/ijo.2011.1245
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Surgery
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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Link
 http://www.spandidos-publications.com/ijo/40/3/889
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