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.