Abstract 4020: The Sox17 gene hypermethylation is useful as a molecular diagnostic application in early stage of gastric cancer

Abstract

Abstract Although minimal invasive treatment is widely accepted for early stage of gastric cancer (GCa), we still do not have any appropriate risk markers to detect residual neoplasia and some potential of recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of gastric neoplasia. Our goal is to find and identify some candidate genes as a treatment marker using genome wide DNA methylation analysis for early stage of gastric cancer (EGC). We studied Methylated CpG Island Amplification Microarray (MCAM) analysis using 12 gastric washes (each 6 before (Pre) and after (Post) endoscopic treatment in same patients). One of them are Sox17. We examined the DNA methylation status of Sox17 in a validation set consisting of 128 washes samples (Pre, 64: Post, 64) at EGC. We next identified functional studies about Sox17 as a putative tumor suppressor gene. Sox17 showed significantly differential methylation between before and after treatment in EGC patient (Sox17, p<0.0001). Moreover, treating GCa cells that lacked Sox17 expression with a methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the gene's expression. Moreover, introduction of exogenous Sox17 into silenced cells suppressed colony formation. Gastric washes based DNA methylation analysis is easy and useful for early detection of recurrence after ER in EGC patients. Our data suggest that silencing of Sox17 occurs frequently in EGC and may play a key role in development and progression of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4020. doi:1538-7445.AM2012-4020