Abstract 3814: Signet-ring cell gastric carcinoma has different epigenetic signature from poorly differentiated gastric carcinoma

Abstract

Abstract Background/Aim: Gastric cancer is divided into differentiated intestinal type and undifferentiated diffuse type by the most widely used Lauren's classification, which appear clearly as dissimilar clinical and epidemiological entities. Undifferentiated diffuse type gastric cancer is also classified into poorly differentiated carcinoma and signet-ring cell carcinoma (SRCC). However, recent evidences suggest early SRCC is an initial, differentiated form of diffuse gastric cancer that may evolve into poorly differentiated carcinoma (PDC). To test the hypothesis that molecular epigenetic signature of SRCC is different from that of PDC in early gastric carcinogenesis, we compared epigenetic methylation profile between SRCC and PDC and found unique epigenetic signature of SRCC. Methods: Six genes (GDNF, ROR-a, KLF7, MINT25, E-cadherin (CDH1), and LINE-1) were identified as sensitive molecular markers of early gastric cancer at a previous study. We evaluated the DNA methylation patterns of 4 gene promoters (GDNF, ROR-a, KLF7 and LINE-1(long interpersed nuclear element-1)) by bisulfite-PCR and pyrosequencing in primary tissues from 33 PDCs and 20 SRCCs as a test group. Then, the methylation status of the 6 genes including MINT25 and E-cadherin (CDH1) was next evaluated in endoscopically biopsied gastric cancer tissues from prospectively collected 21 PDCs and 22 SRCCs as a validation group. Results: In the test group, quantitative methylation levels of 3 genes (GDNF, ROR-a, and LINE-1) of SRCCs were significantly different from those of PDCs. MINT25, E-cadherin including the above 4 genes were next evaluated in the validation group. We confirmed the significant different levels of methylations of prospectively collected SRCCs from PDCs. Compared to PDCs, SRCCs showed the lower level of methylations for GDNF (17.7% vs. 31.0%, p = 0.001) and ROR-a (14.4% vs. 28.0%, p = 0.001) genes. Interestingly, however, the methylation level of E-cadherin was higher in SRCCs than that of PDCs (26.8% vs. 20.5%, p = 0.009). Methylaion levels of LINE-1 (63.0% vs. 60.5%), MINT25 (31.1% vs. 34.3%) and KLF7 (10.2% vs. 18.1%) in SRCCs were not significantly different from those of PDCs. Conclusion: Our results identified unique methylation patterns of SRCCs distinguished from PDCs, suggesting different molecular epigenetic signature of SRCC in gastric carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3814. doi:10.1158/1538-7445.AM2011-3814