PT - JOURNAL ARTICLE AU - Li, Ziyu AU - Gao, Xiangyu AU - Peng, Xinxin AU - May Chen, Mei-Ju AU - Li, Zhe AU - Wei, Bin AU - Wen, Xianzi AU - Wei, Baoye AU - Dong, Yu AU - Bu, Zhaode AU - Wu, Aiwen AU - Wu, Qi AU - Tang, Lei AU - Li, Zhongwu AU - Liu, Yiqiang AU - Zhang, Li AU - Jia, Shuqin AU - Zhang, Lianhai AU - Shan, Fei AU - Zhang, Ji AU - Wu, Xiaojiang AU - Ji, Xin AU - Ji, Ke AU - Wu, Xiaolong AU - Shi, Jinyao AU - Xing, Xiaofang AU - Wu, Jianmin AU - Lv, Guoqing AU - Shen, Lin AU - Ji, Xuwo AU - Liang, Han AU - Ji, Jiafu TI - Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy AID - 10.1126/sciadv.aay4211 DP - 2020 Feb 01 TA - Science Advances PG - eaay4211 VI - 6 IP - 9 4099 - http://advances.sciencemag.org/content/6/9/eaay4211.short 4100 - http://advances.sciencemag.org/content/6/9/eaay4211.full SO - Sci Adv2020 Feb 01; 6 AB - Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.