Abstract
Abstract Background: Gastric cancer was characterized by frequent somatic copy number alterations and high genomic instability, yet the significance of genomic instability and its changes implicated by drug treatment in advanced gastric cancer (AGC) remain unclear. In this study, we investigated genomic instability changes of circulating tumor DNA (ctDNA). Methods: A total of 101 plasmas and paired blood cells from 26 patients with AGC before (N=26) and after (N=75) treatment were prospectively collected. Plasma ctDNA was separated and assessed for copy number variations (CNV) by whole genome sequencing (WGS), and we assessed the correlation between genomic indexes and therapeutic response. Results: Genomic instability with diverse patterns was observed in 20 of 26 patients (77%) prior to drug treatment. For patients with high (N=20) level genomic instability prior to drug treatment, the response rate (55%, 11/20) was significantly higher than that (17%, 1/6) in patients with low level (N=6) genomic instability (P=0.17). Notably, genomic instability changed with the administration of drugs, which reflected its correlation with therapeutic response. All ctDNAs (94%, 14/15) collected at the time of partial response (PR) after treatment displayed low-genomic instability. However, 52% ctDNAs (13/25) collected at the time of progressive disease (PD) after treatment showed high-level genomic instability. Furthermore, several patterns of CNV were categorized in ctDNAs. CNV pattern after acquiring drug resistance were largely unchanged with respect to CNV baseline patterns. Conclusions: Genomic instability based on ctDNA can be used to predict and monitor therapeutic response in gastric cancer, although validation in larger cohort would be necessary. Citation Format: Zuhua Chen, Cheng Zhang, Beifang Li, Yunyun Niu, Limeng Chen, Mengqi Zhang, Jing Yang, Sijia Lu, Jing Gao, Lin Shen. Genomic instability changes of circulating tumor DNA reflect the responses to chemotherapy or targeted therapy in advanced gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 424.
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