title: Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches.
abstract: 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.
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kusakabe
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kutomi
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Emoto
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Aki
authors.affiliation: Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kage
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Hamano
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sano
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukami
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Murakawa
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakajima
authors.affiliation: Department of General Thoracic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takamoto
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ota
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.affiliation: Department of Respiratory Medicine, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ohishi
authors.affiliation: Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Daiya
authors.initials: D
authors.lastname: Takai
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D016000:Cluster Analysis; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C508073:G0S2 protein, human