| Accession |
PRJCA001620 |
| Title |
Multi-omics Characterization of Gastric Cancer Evolution under Neoadjuvant Chemotherapy |
| Relevance |
Medical |
| Data types |
Whole genome sequencing
Exome
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Homo sapiens
|
| Description |
Neoadjuvant chemotherapy is a common treatment option for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, largely due to 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 post-treatment 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 vs. nonresponse tumors and pre- vs. post-treatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by in vitro drug response data and potentially through the inhibition of cell cycle; and MYC amplification correlated with treatment sensitivity whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes the tumor immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens. |
| Sample scope |
Multiisolate |
| Release date |
2019-09-25 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 32133402
|
Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy
|
Science Advances
|
10.1126/sciadv.aay4211
|
2020
|
|
|
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
31870805
|
|
| The Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding
|
|
ZYLX201701
|
|
| "San Ming" Project of Shenzhen City
|
|
SZSM201612051
|
|
|
|
| Submitter |
Xiangyu
Gao (xiangyugao@hsc.pku.edu.cn)
|
| Organization |
Beijing Cancer Hospital |
| Submission date |
2019-07-25 |
