Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation
文献类型：期刊论文
| 作者 | Jin, Ying1,2,3,4; Bao, Hua5; Le, Xiuning6; Fan, Xiaojun5; Tang, Ming6; Shi, Xun1,2,3; Zhao, Jun1,2,3; Yan, Junrong7; Xu, Yang5; Quek, Kelly6 |
| 刊名 | ONCOGENE
 |
| 出版日期 | 2020-02-01 |
| 卷号 | 39 |
| ISSN号 | 0950-9232 |
| DOI | 10.1038/s41388-019-1104-z |
| 通讯作者 | Chen, Ming() ; Zhang, Jianjun() ; Yu, Xinmin(yuxm@zjcc.org.cn) |
| 英文摘要 | EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Systematic genetic analysis is important to understand drug-resistant mechanisms; however, the clinical significance of co-occurring genetic alterations at baseline, co-acquired mutations at progressive disease (PD), and the clonal evolution remain underinvestigated. We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole-exome sequencing to infer the clonal evolution patterns. We observed a domain-dependent effect of PIK3CA mutation at baseline on patient progression-free survival (PFS). In addition, at baseline, 9q34.3/19p13.3 (NOTCH1/STK11/GNA11) showed a co-deletion pattern, which was associated with a significantly worse PFS (p = 0.00079). T790M-postive patients with other concurrent acquired oncogenic mutations had a significantly shorter PFS (p = 0.005). Besides acquired T790M mutation, chromosomal instability (CIN) related genes, including AURKA and TP53 alterations, were the most frequently acquired events. CIN significantly increased during TKI treatment in T790M-negative patients and is a candidate resistance mechanism to the first-generation TKIs. Clonal evolution analyses suggest that the composition and relationship among resistant subclones, particularly relationship with T790M subclone, affect patients' outcomes. Overall, our findings of novel co-occurring alterations and clonal evolution patterns can be served as predictive biomarkers to stratify patients and help to better understand the drug-resistant mechanism to TKIs. |
| WOS关键词 | GROWTH-FACTOR RECEPTOR ; TYROSINE KINASE INHIBITORS ; INTRATUMOR GENETIC-HETEROGENEITY ; 1ST-LINE TREATMENT ; CLINICAL IMPACT ; OPEN-LABEL ; RESISTANCE ; PIK3CA ; ADENOCARCINOMAS ; DIVERSITY |
| 资助项目 | National Natural Science Foundation of China[81702248] ; National Natural Science Foundation of China[81672972] ; Zhejiang Medical and Health Science and Technology Project[2018KY309] ; Zhejiang Medical and Health Science and Technology Project[2017KY239] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000516579800002 |
| 资助机构 | National Natural Science Foundation of China ; Zhejiang Medical and Health Science and Technology Project |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/103971]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Chen, Ming; Zhang, Jianjun; Yu, Xinmin |
| 作者单位 | 1.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou, Zhejiang, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China 3.Zhejiang Canc Hosp, Hangzhou, Zhejiang, Peoples R China 4.Zhejiang Key Lab Radiat Oncol, Hangzhou, Zhejiang, Peoples R China 5.Geneseeq Technol Inc, Translat Med Res Ctr, Toronto, ON, Canada 6.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA 7.Nanjing Geneseeq Technol Inc, Nanjing, Jiangsu, Peoples R China 8.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA 9.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA 10.Imperial Coll London, ICTEM, Div Canc, Dept Surg & Canc, London W12 0NN, England |
| 推荐引用方式 GB/T 7714 | Jin, Ying,Bao, Hua,Le, Xiuning,et al. Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation[J]. ONCOGENE,2020,39. |
| APA | Jin, Ying.,Bao, Hua.,Le, Xiuning.,Fan, Xiaojun.,Tang, Ming.,...&Yu, Xinmin.(2020).Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation.ONCOGENE,39. |
| MLA | Jin, Ying,et al."Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation".ONCOGENE 39(2020). |
入库方式： OAI收割
来源：合肥物质科学研究院
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