686P - Overall Survival (OS) to First- and Second-Line Chemotherapy Associated with Mrna Expression of Multiple Myeloma Set (MMSET) Domain, P53-Binding Protein 1 (53bp1) and Breast Cancer Susceptibility Gene 1 (BRCA1) in advanced Gastric Cancer Patients (P)

Abstract

ABSTRACT Background Low BRCA1 expression enhances sensitivity to platinum, while high levels increase sensitivity to taxanes (Quinn et al. Cancer Res 2003). In response to cisplatin-induced DNA double strand breaks (DSBs), MDC1 binds to γH2AX, promoting DSB repair by 53BP1 and BRCA1. MMSET is required for the accretion of 53BP1, PIAS4 and Ubc9 to DSB sites. We hypothesized that the mRNA expression of these components of the MDC1-MMSET-53BP1 pathway could impact the predictive model based on BRCA1 mRNA expression (Wei et al. JNCI 2011). Methods Tumor samples were obtained from 132 advanced gastric cancer p treated with first-line FOLFOX, 58 of whom also received second-line docetaxel. mRNA expression of MDC1, MMSET, 53BP1, PIAS4, Ubc9 and BRCA1 was analyzed by real-time PCR. Results A close correlation was found between MMSET and BRCA1 (r = 0.28; P = 0.002), 53BP1 (r = 0.54; p Conclusions Longer OS to FOLFOX was associated with low levels of both MMSET and 53BP1, while longer OS to second-line docetaxel was associated with high levels of both MMSET and BRCA1. MMSET, together with 53BP1 or BRCA1 can be useful for customizing chemotherapy in advanced gastric cancer p. Disclosure All authors have declared no conflicts of interest.