Abstract 643: Gene methylation as a novel marker in gastric cancer.

Abstract

Abstract Introduction: Epigenetics is one of the major cause of cancer. Several studies have shown the relation between gastric cancer and DNA methylation but it lacks coherence to use as a biomarker. Also there is a lot of genes have not reveled correlation between gastric cancer and DNA methylation. Here, we analyze the correlation between DNA methylation and gene expression in gastric cancer to use as a novel biomarker. Method: Gastric cancer and matched normal gastric tissues were obtained who received gastrectomy in Seoul national university. More than 70 % of tumor share tissues were selected for this study. Nine genes (FAM58A, MAL, TMEM220, MMP28, C2orf3, IL-19, RIN2, HOPX, RGS6) expression level were analyzed using 30 pairs of gastric cancer, normal gastric tissues We then selected genes showing distinct difference mRNA expression level between gastric cancer and gastric tissues to analyze DNA methylation level using bisulfite modification. After that we analyze gene expression level and methylation level using 10 gastric cancer cell line(MKN28, AGS, KATOIII, ect..)to compare with gastric cancer tissues Result: Advanced research of this study performed MIRA for analyze DNA methylation level and Real-time pcr to know mRNA expression level using three snap-frozen gastric cancer and matched normal gastric tissue. This study identified that FAM58A, RYR2, SLC9A7, GHSR, HIST1H4E, MAL, TMEM220,C2orf3, MMP28, EPOR etc sixteen genes were hypermethylated in gastric cancer and there were correlation between methylation level and mRNA expression level Also this study found ten hypomethylated genes (STAC, IL19,HYDIN, C1orf162, OR2J2, RIN2,HOPX, RGS6,MOCS1 ect) using three gastric tissue samples. These genes also associated with mRNA expression level comparison between gastric cancer and normal gastric tissues. Among the hypermethylated genes, we analyzed FAM58A, MAL, TMEM220, MMP28, C2orf3 genes MAL(p<0.00004), TMEM220(P<0.0002), MMP28(P<0.00011) mRNA expression level were significantly down-regulated in gastric cancer tissues.. Especially MAL gene is remarkably down-regulated in all 30 samples of gastric cancer tissues. Additionally we analyzed four hypomethylated genes (hand IL-19, RIN2, HOPX, RGS6). RIN2, HOPX, RGS6) but RIN2, HOPX, RGS6 genes mRNA expression level differ in each gastric cancer tissues The other hand IL-19 have shown different mRNA expression level what we expected in advanced study. Except three dramatically up-regulated tissues, almost the others mRNA expression level were down-regulated in 30 gastric cancer tissue samples(p<0.027) Conclusion: Our finding will provide valuable data for development of the useful gastric cancer methylation marker and understanding of correlation between methylation and mRNA expression level in gastric cancer. Furthermore MAL gene case, we expect it could be a gastric cancer marker not only methylation analysis but also mRNA expression level analysis. Citation Format: Boram Choi, Tae-Su Han, Ji-Yeon Lee, Sunmin Lee, Seong-Ho Kong, Hyuk-Jun Lee, Young-Joon Kim, Han-Kwang Yang. Gene methylation as a novel marker in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 643. doi:10.1158/1538-7445.AM2013-643