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タイトル: Different histological types of non-small cell lung cancer have distinct folate and DNA methylation levels
著者: Jin, Ming Ji
Kawakami, Kazuyuki
Fukui, Yousuke
Tsukioka, Sayaka
Oda, Makoto
Watanabe, Go
Takechi, Teiji
Oka, Toshinori
Minamoto, Toshinari link image link image
川上, 和之
小田, 誠
渡邊, 剛
源, 利成
発行日: 2009年12月
出版社(者): Japanese Cancer Association = 日本癌学会
雑誌名: Cancer Science
ISSN: 1347-9032
巻: 100
号: 12
開始ページ: 2325
終了ページ: 2330
抄録: Aberrant DNA methylation is a commonly observed epigenetic change in lung cancer. Folate has been suggested to play a role in the homeostasis of DNA methylation and has also been implicated in cancer chemotherapy. We investigated a possible role for folate in DNA methylation by measuring folate concentrations in tumors and adjacent normal tissues from 72 non-small cell lung cancer (NSCLC) patients. These were compared to DNA methylation levels and to clinicopathological features. Folate concentrations were determined as the sum of 5,10-methylenetetrahydrofolate and tetrahydrofolate. The MethyLight assay was used to quantitate methylation in promoter regions of P16(CDKN2A), APC, CDH13, RARB, RASSF1, RUNX3, and MYOD1. Methylation of LINE-1 repeats was used as a surrogate for global methylation. Folate levels in tumors correlated positively with LINE-1, CDH13, and RUNX3 methylation. Folate concentrations and methylation of LINE-1, RASSF1, and RUNX3 were significantly higher in adenocarcinoma compared to squamous cell carcinoma (SCC). Two sets of array-based data retrieved from the Gene Expression Omnibus consistently showed that expression of FOLR1, a folate transport enzyme, and GGH, an enzyme that prevents folate retention, were higher and lower, respectively, in adenocarcinomas compared to SCC. This was independently validated by quantitative RT-PCR in 26 adenocarcinomas and 13 SCC. Our results suggest that folate metabolism plays a role in aberrant DNA methylation in NSCLC. The histological subtype differences in folate concentration and DNA methylation observed here were associated with distinct expression patterns for folate metabolizing enzymes. These findings may have clinical applications for histology-directed chemotherapy with fluoropyrimidine and anti-folates in NSCLC. © 2009 Japanese Cancer Association.
DOI: 10.1111/j.1349-7006.2009.01321.x
URI: http://hdl.handle.net/2297/20147
関連URI: http://www3.interscience.wiley.com/journal/122577084/abstract
資料種別: Journal Article
権利関係: The definitive version is available at www.blackwell-synergy.com
版表示: publisher
出現コレクション:1. 査読済論文

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