Genomic characterization of Chinese locally advanced or metastatic gastric cancer.

Xiaotian Zhang Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China info_outline Xiaotian Zhang, Yakun Wang, Shi Xinying, Changsong QI, Zhi Peng, Tong Xie, Dan Liu, Siyuan Cheng, Panpan Zhang, Yiqun Zhang, Qianhui Wan, Nana Hu, Zhihua Pei, Dongliang Wang, Lin Shen

Authors Xiaotian Zhang Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China info_outline Xiaotian Zhang, Yakun Wang, Shi Xinying, Changsong QI, Zhi Peng, Tong Xie, Dan Liu, Siyuan Cheng, Panpan Zhang, Yiqun Zhang, Qianhui Wan, Nana Hu, Zhihua Pei, Dongliang Wang, Lin Shen Organizations Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China, Department of Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, China, ChosenMed Technology Co., Ltd., Beijing, China, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China Abstract Disclosures Research Funding No funding received Background: The comprehensive molecular characterization of gastric cancer has been uncovered by The Cancer Genome Atlas (TCGA) research work. However, the genomic feature of Chinese locally advanced or metastatic gastric cancer has been seldom reported. This study aims to explore the genomic landscape of Chinese locally advanced or metastatic gastric cancer. Methods: 556 locally advanced or metastatic gastric cancer patients were enrolled in this study and 245 eligible patients with adequate clinicopathological data were analyzed. The baseline tumor tissues and corresponding blood were collected and target-captured sequencing were applied. Both tumor fragments and fragmented genomic DNA were subjected to the NGS platform aiming a panel covering exon regions of 599 genes. Genetic alterations were analyzed to investigate the mutational profile of Chinese locally advanced or metastatic gastric cancer. Results: The top 10 common tumor driver gene alterations among all cases were TP53, ARID1A, CDH1, ARID1B, NOTCH1, ATRX, AR, RAD50, SMAD4 and ZFHX3. TP53 mutation was detected in 70% of all cases, which was significantly higher than that in the TCGA non-Asian (44%) and Asian (46%) advanced gastric cancer patients. 90% (20/22) MSI-H patients had high TMB values, and 32.7% (20/61) high TMB patients were MSI-H. Neither TMB values nor MSI scores was statistically different between patients with response (CR+PR) and without response (PD+SD) to chemotherapy (p = 0.366, 0.436). While the combination of SPTA1 and TP53 mutation was significantly more frequent in response (CR+PR) than non-response (PD+SD) patients. Conclusions: The mutated driver genes of Chinese locally advanced or metastatic gastric cancer were different from the TCGA advanced gastric cancer. The combination of TP53 and and SPTA1 could identify the patients’ response to chemotherapy.