title: Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell             lung cancer.
abstract: Genome-wide DNA hypomethylation and gene hypermethylation play important             roles in instability and carcino-genesis. Methylation in long interspersed nucleotide             element 1 (LINE-1) is a good indicator of the global DNA methylation level within             a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like             growth factor binding protein 7 (IGFBP7) are known to be hypermethylated in various             malignancies. The aim of the present study was to assess the precise methylation             levels of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer (NSCLC)             using a pyrosequencing assay. Methylation of all regions was examined in 56 primary             NSCLCs using a pyrosequencing assay. Changes in mRNA expression levels of SLIT2,             MAL and IGFBP7 were measured before and after treatment with a demethylating agent.             Methylation of these genes was also examined in 9 lung cancer cell lines using             RT-PCR and a pyrosequencing assay. Frequencies of hypomethylation of LINE-1 and             hypermethylation of SLIT2, MAL and IGFBP7, defined by predetermined cut off values,             were 55, 64, 46 and 54% in NSCLCs, respectively and exhibited tumor-specific features.             The hypermethylation of all genes was well correlated with changes in expression.             The methylation level and frequency of MAL were significantly higher in smokers             and in patients without EGFR mutations. Through accurate measurement of methylation             levels using pyrosequencing, hypomethylation of LINE-1 and hypermethylation of             SLIT2, MAL and IGFBP7 were frequently detected in NSCLCs and associated with various             clinical features. Analysis of the methylation profiles of these genes may, therefore,             provide novel opportunities for the therapy of NSCLCs.
authors: Department of Thoracic Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556, Japan. smakoto@kumamoto-u.ac.jp
authors: Makoto
authors: M
authors: Suzuki
authors: Kenji
authors: K
authors: Shiraishi
authors: Ayami
authors: A
authors: Eguchi
authors: Koei
authors: K
authors: Ikeda
authors: Takeshi
authors: T
authors: Mori
authors: Kentaro
authors: K
authors: Yoshimoto
authors: Yasuomi
authors: Y
authors: Ohba
authors: Tatsuya
authors: T
authors: Yamada
authors: Takaaki
authors: T
authors: Ito
authors: Yoshifumi
authors: Y
authors: Baba
authors: Hideo
authors: H
authors: Baba
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000098552:Slit Homolog 2 Protein
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C569026:MAL protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009419:Nerve Tissue Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D000098552:Slit Homolog 2 Protein
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