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Genomic Landscape and Clinical Impact of MTAP Loss in Driver-Positive NSCLC: Insights From a Large-Scale Real-World Chinese Cohort. 期刊论文

编号：

F83F94C2DA6E15C16709844EA6C98519
作者：

Wei Qianhui#^[1,2,3,4]Wang Youhui#^[1,2,3,4]Hou Ting^[5];Wang Qianxi^[1,2,3,4];Lu Bo^[1,2,3,4];Zhang Lu^[6];Liu Chenglin^[5];Kuang Ting^[5];Li Xinyan^[1,2,3,4];Jiang He^[1,2,3,4];Zhao Jiayi^[1,2,3,4];Sun Yuan^[5];Yue Dongsheng(岳东升)^[1,2,3,7]Jiang Richeng^{[1,2,3,8,9,10]};Wang Xinyue(王心悦)*^[1,2,3,11]
地址：

(Wei Qianhui)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Wang Youhui)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Hou Ting)Burning Rock Biotech, Guangzhou, People's Republic of China.,(Wang Qianxi)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Lu Bo)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Zhang Lu)Center for Precision Cancer Medicine and Translational Research, Tianjin Cancer Hospital Airport Hospital, Tianjin, People's Republic of China.,(Liu Chenglin)Burning Rock Biotech, Guangzhou, People's Republic of China.,(Kuang Ting)Burning Rock Biotech, Guangzhou, People's Republic of China.,(Li Xinyan)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Jiang He)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Zhao Jiayi)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Sun Yuan)Burning Rock Biotech, Guangzhou, People's Republic of China.,(Yue Dongsheng)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Department of Lung Cancer, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China.,(Jiang Richeng)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China; Department of Medical Oncology, Beijing Hospital, National Center for Gerontology, National Clinical Research Center for Gerontology, Beijing, People's Republic of China; The Key Laboratory of Geriatrics of NHC, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.,(Wang Xinyue)Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People's Republic of China; Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China; Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China; Center for Precision Cancer Medicine and Translational Research, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China. Electronic address: xwang18@tmu.edu.cn.
语种：

英文
期刊：

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer ISSN：1556-1380 2026 年 (104077 - ) ; 2026-Jul-06
收录：
关键词：

CDKN2A loss EGFR-TKI MTAP loss Non–small cell lung cancer Targeted therapy
摘要：

MTAP loss is a frequent genomic event in NSCLC, yet its clinical and therapeutic implications in oncogene-driven disease remain incompletely understood.;We analyzed genomic profiles of 6492 Chinese patients with NSCLC from a real-world database and evaluated survival outcomes in 173 treatment-naïve, driver-positive patients receiving first-line targeted therapies. Associations of MTAP loss with clinicopathologic characteristics, co-mutations, and outcomes were assessed, with particular attention to its interplay with CDKN2A loss.;MTAP loss was identified in 10.4% of the overall cohort and was enriched in advanced stage and tumors harboring oncogenic drivers, including EGFR mutations, ALK fusions, and amplifications of MET and ERBB2. Co-deletion with CDKN2A was highly prevalent in MTAP-loss tumors (92.3%). Structurally, MTAP loss was predominantly complete (87.8%), with the remaining cases mainly comprising partial losses involving exon 8 (10.6%). A high concordance (92.1%) was observed between next-generation sequencing and immunohistochemistry for the identification of MTAP loss. In driver-positive patients, MTAP loss was associated with a lower response rate and shorter progression-free survival and overall survival, especially in EGFR-mutant patients treated with third-generation EGFR-tyrosine kinase inhibitors. Combined MTAP/CDKN2A analysis revealed a prognostic gradient, with dual loss conferring the worst outcomes and remaining an independent predictor in multivariable models.;MTAP loss defines a distinct molecular subset of NSCLC and serves as a robust adverse prognostic biomarker in EGFR-mutant disease treated with targeted therapies. These findings support integrating MTAP status into risk stratification and exploring combination strategies that incorporate PRMT5 or MAT2A inhibition.;
推荐引用方式
GB/T 7714：

Wei Qianhui,Wang Youhui,Hou Ting, et al. Genomic Landscape and Clinical Impact of MTAP Loss in Driver-Positive NSCLC: Insights From a Large-Scale Real-World Chinese Cohort. [J].Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer,2026:104077-.
APA：

Wei Qianhui,Wang Youhui,Hou Ting,Wang Qianxi,&Wang Xinyue.(2026).Genomic Landscape and Clinical Impact of MTAP Loss in Driver-Positive NSCLC: Insights From a Large-Scale Real-World Chinese Cohort. .Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer:104077-.
MLA：

Wei Qianhui, et al. "Genomic Landscape and Clinical Impact of MTAP Loss in Driver-Positive NSCLC: Insights From a Large-Scale Real-World Chinese Cohort." .Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer(2026):104077-.
入库时间：

10/27/2026 9:22:26 PM
更新时间：

10/27/2026 9:22:26 PM

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