Aim: Although minimal invasive treatment is accepted for gastric cancer, we still do not have any appropriate risk markers to detect residual neoplasia and recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for detection of neoplasia. Our goal is to find some candidate genes as a treatment marker using genome wide DNA methylation analysis for early gastric cancer (EGC). Methods and Results: 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 is BARHL2. We examined the DNA methylation status of BARHL2 in a validation set consisting of 128 washes samples (Pre, 64: Post, 64) at EGC. We next identified functional studies about BARHL2 as a putative tumor suppressor gene. Treating GCa cells that lacked BARHL2 expression with a methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the gene's expression. Introduction of exogenous BARHL2 into silenced cells suppressed colony formation. Moreover, BARHL2 showed significantly differential methylation between before and after treatment in EGC patient (BARHL2, p<0.0001). Discussion: Our data suggest that silencing of BARHL2 occurs frequently in EGC and may play a key role in development and progression of the disease.

Citation Format: Yoshiyuki Watanabe, Ritsuko Oikawa, Hiroyuki Yamamoto, Fumio Itoh. Hypermethylation of BARHL2 gene is useful as a molecular marker in early stage of gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1062. doi:10.1158/1538-7445.AM2015-1062

©2015 American Association for Cancer Research.
2015