LAUSR

Epigenetic dysregulation is a common characteristic of cancer, including gastric cancer(GC), which ultimately contributes to the development and progression of GC. Sequencing of cancer genomes has revealed frequent mutations in epigenetic regulators, particularly chromatin remodelers and histone modifiers, and disordered chromatin regulation has emerged as a distinct mechanism contributing to tumor development. As a highly conserved class of epigenome readers, BRD4 is a member of the BET (bromodomain and extra-terminal domain) family that recognizes and binds acetylated histones H3 and H4 and influences gene regulation. Small molecule BET inhibitors prevent binding of BET proteins to acetylated histones and inhibit transcriptional activation of BET target genes. BET inhibitors attenuate cell growth and survival in several hematologic cancer models, partially through the down-regulation of the critical oncogene, c-Myc. We would like to elucidate the sensitivity to I-BET151 and its relationship with genetic/epigenetic alterations to identify predictive biomarkers in 49 gastric cancer cell lines. Anticancer effect of small molecular inhibitor of the BET family, GSK1210151A (I-BET151, GSK, PA, USA), was treated for 6 days and assessed using CCK-8 assay. For exploring predictive biomarkers, we analyzed genetic and molecular characterization of BRD4-related genes using whole exome sequencing (WES), RNA sequencing and western blots. As a result, ARID1A deletion (SNU-5 and YCC-6) and single nucleotide variant (14/49, 28.5%) were correlated with decreased protein expression (p 5 uM: 13 cell lines). Then, we analyzed Differentially Expressed Gene (DEG) in each group and selected about 600 genes (FDR Citation Format: Sun Kyoung Kang, Tae Soo Kim, Woo Sun Kwon, Jae Kyung Roh, Ho-Yeong Lim, Hyun Cheol Chun, Sun Young Rha. Inhibition of BET bromodomain, epigenetic regulator, as an effective therapeutic approach for gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5069. doi:10.1158/1538-7445.AM2017-5069