Frequent silencing of the candidate tumor suppressor TRIM 58 by promoter methylation in early-stage lung adenocarcinoma 2

• Material Type: 博士論文
• ISSN: 1949-2553
• Title: Frequent silencing of the candidate tumor suppressor TRIM 58 by promoter methylation in early-stage lung adenocarcinoma
• Volume: 8 2
• Author/Editor: Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watanabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei
• Author Heading: Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watanabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei
• Publication, Distribution, etc.: Impact Journals
• Publication Date: 2016-12-01
• Publication Date (W3CDTF): 2016-12-01
• Alternative Title: 早期肺腺癌において癌抑制遺伝子TRIM 58はプロモーター領域のメチル化により高頻度に抑制される
• Periodical title: Oncotarget
• Degree grantor/type: 徳島大学
• Date Granted: 2017-03-21
• Date Granted (W3CDTF): 2017-03-21
• Dissertation Number: 甲第3024号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3024号
• Text Language Code: eng
• Subject Heading: TRIM58; early-stage lung adenocarcinoma; tumor suppressor gene; methylation; smoking status
• Target Audience: 一般
• Note (General): In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.
• DOI: info:doi/10.18632/oncotarget.13761; https://doi.org/info:doi/10.18632/oncotarget.13761
• Persistent ID (NDL): info:ndljp/pid/10370493; https://dl.ndl.go.jp/pid/10370493
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2017-07-03T04:10:06+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/110044
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp