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

Authors
 Sunwoo Lee  ;  Taejeong Oh  ;  Hyuncheol Chung  ;  Sunyoung Rha  ;  Changjin Kim  ;  Youngho Moon  ;  Benjamin D. Hoehn  ;  Dongjun Jeong  ;  Seunghoon Lee  ;  Namkyu Kim  ;  Chanhee Park  ;  Miae Yoo  ;  SungWhan An 
Citation
 INTERNATIONAL JOURNAL OF ONCOLOGY, Vol.40(3) : 889-898, 2012 
Journal Title
 INTERNATIONAL JOURNAL OF ONCOLOGY 
ISSN
 1019-6439 
Issue Date
2012
MeSH
Biomarkers, Tumor/genetics* ; Caco-2 Cells ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Colorectal Neoplasms/genetics* ; Colorectal Neoplasms/pathology ; CpG Islands ; DNA Methylation* ; Down-Regulation ; Epigenomics/methods ; Female ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; Laminin/genetics* ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis/methods ; Receptors, GABA-A/genetics*
Keywords
Biomarkers, Tumor/genetics* ; Caco-2 Cells ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Colorectal Neoplasms/genetics* ; Colorectal Neoplasms/pathology ; CpG Islands ; DNA Methylation* ; Down-Regulation ; Epigenomics/methods ; Female ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; Laminin/genetics* ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis/methods ; Receptors, GABA-A/genetics*
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.
Full Text
http://www.spandidos-publications.com/ijo/40/3/889
DOI
22038115
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Kyu(김남규) ORCID logo https://orcid.org/0000-0003-0639-5632
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Chan Hee(박찬희)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90502
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