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Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches
Author(s) -
Kusakabe Masashi,
Kutomi Tomoko,
Watanabe Kousuke,
Emoto Noriko,
Aki Naomi,
Kage Hidenori,
Hamano Emi,
Kitagawa Hiroshi,
Nagase Takahide,
Sano Atsushi,
Yoshida Yukihiro,
Fukami Takeshi,
Murakawa Tomohiro,
Nakajima Jun,
Takamoto Shinichi,
Ota Satoshi,
Fukayama Masashi,
Yatomi Yutaka,
Ohishi Nobuya,
Takai Daiya
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24947
Subject(s) - dna methylation , methylation , lung cancer , epigenetics , biology , cancer , bisulfite sequencing , cancer research , gene , methylated dna immunoprecipitation , differentially methylated regions , in silico , illumina methylation assay , microbiology and biotechnology , genetics , gene expression , oncology , medicine
Epigenetic changes can lead to abnormal expression of genes in cancer, and several genes have been reported to have aberrant promoter DNA methylation in non‐small‐cell lung cancer (NSCLC). We identified aberrantly methylated genes in NSCLC by combination of in silico and experimental approaches. We first applied bioinformatics, and from microarray datasets, we selected genes with low expression and having functions related to cancer. Next, combined bisulfite restriction analysis was carried out in 10 pooled resected lung cancer tissues to screen for genes that were aberrantly methylated, and the methylation ratio (the fraction of methylated DNA in extracted DNA from a cancer tissue sample) was quantified using quantitative analysis of methylated alleles. We identified 8 methylated genes ( ARPC1B , DNAH9 , FLRT2 , G0S2 , IRS2 , PKP1 , SPOCK1 and UCHL1 ) previously unreported in NSCLC. Analyses of methylation profiles of 101 resected lung cancer tissue samples revealed quantitatively low methylation in whole, methylation ratios were almost less than 30% even in the methylated samples, and no significant correlation to prognosis after 2 years of follow‐up using hierarchical clustering. DNA methylation of G0S2 gene was significantly more frequent in squamous lung cancer ( n = 18, mean of methylation ratios: 15%) compared with nonsquamous lung cancer ( n = 83, mean of methylation ratios: 2.6%) (Mann‐Whitney U test, p < 0.001). DNA methylation of G0S2 can be an important biomarker for squamous lung cancer.