Kiichi Sugimoto1,2, Tomoaki Ito3,4, Alicia Hulbert3, Chen Chen3, Hajime Orita4, Masahiro Maeda5, Hiroshi Moro5, Takeo Fukagawa6, Toshikazu Ushijima5, Hitoshi Katai6, Ryo Wada7, Koichi Sato4, Kazuhiro Sakamoto8, Wayne Yu9, Michael Considine10, Leslie Cope10, Malcolm V Brock3. 1. Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Blalock 240, Baltimore, MD, 21287, USA. ksugimo@juntendo.ac.jp. 2. Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan. ksugimo@juntendo.ac.jp. 3. Department of Surgery, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 600N. Wolfe Street, Blalock 240, Baltimore, MD, 21287, USA. 4. Department of Surgery, Juntendo University Shizuoka Hospital, Shizuoka, Japan. 5. Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan. 6. Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan. 7. Department of Pathology, Juntendo University Shizuoka Hospital, Shizuoka, Japan. 8. Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan. 9. Microarray Core Facility, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. 10. Experimental and Computational Genomics Core, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Abstract
BACKGROUND: Although primary (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. We hypothesized that there would be distinct differences in DNA methylation patterns that would occur during carcinogenesis of RGC and PGC, and that the differences in methylation patterns may help identify the primary factor contributing to chronic inflammation in patients with RGC. METHODS: We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients using the Infinium HumanMethylation450 Beadchip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. RESULTS: We found that in our training cohort of 48 patients, the most variable genes from the gastric cancer tissues identified by the Infinium HumanMethylation450 Beadchip clustered the resultant heatmap into high and low methylation groups. On multivariate analysis, PGCs contributed significantly to the high methylation group (p = 0.004, OR 12.33), which suggested that the promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the EPB41L3 gene, chosen because of its high β value on microarray analysis in the gastric cancer tissues, had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. CONCLUSIONS: This study demonstrated that promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of the absence of Helicobacter pylori on the reduced DNA methylation in the remnant stomach.
BACKGROUND: Although primary (PGC) and remnant gastric cancers (RGC) both originate from the same gastrointestinal organ, they have very distinct clinicopathological behaviors. We hypothesized that there would be distinct differences in DNA methylation patterns that would occur during carcinogenesis of RGC and PGC, and that the differences in methylation patterns may help identify the primary factor contributing to chronic inflammation in patients with RGC. METHODS: We investigated the genome-wide DNA methylation patterns of PGC and RGC tissues from 48 patients using the Infinium HumanMethylation450 Beadchip assay. The results were validated by quantitative methylation-specific PCR (qMSP) in separate, independent cohorts. RESULTS: We found that in our training cohort of 48 patients, the most variable genes from the gastric cancer tissues identified by the Infinium HumanMethylation450 Beadchip clustered the resultant heatmap into high and low methylation groups. On multivariate analysis, PGCs contributed significantly to the high methylation group (p = 0.004, OR 12.33), which suggested that the promoter methylation status in PGC is higher than that in RGC. Supporting this conclusion was the finding that in a separate qMSP analysis in a test cohort, the EPB41L3 gene, chosen because of its high β value on microarray analysis in the gastric cancer tissues, had significantly higher DNA promoter methylation in cancer tissues in the validation PGC tissues than in RGC. CONCLUSIONS: This study demonstrated that promoter methylation status in PGC is higher than in RGC. This result may reflect the effects of the absence of Helicobacter pylori on the reduced DNA methylation in the remnant stomach.
Authors: N Uemura; S Okamoto; S Yamamoto; N Matsumura; S Yamaguchi; M Yamakido; K Taniyama; N Sasaki; R J Schlemper Journal: N Engl J Med Date: 2001-09-13 Impact factor: 91.245
Authors: Yazhuo Li; Yunsheng Yang; Youyong Lu; James G Herman; Malcolm V Brock; Po Zhao; Mingzhou Guo Journal: Gastric Cancer Date: 2014-04-21 Impact factor: 7.370
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