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The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients

文献类型：期刊论文

作者Cai, Lei7,8; Chen, Yong1; Tong, Xiaoling2; Wu, Xue2; Bao, Hua2; Shao, Yang5,6; Luo, Zhuang4; Wang, Xuming4; Cao, Yang3
刊名INTERNATIONAL JOURNAL OF CANCER
出版日期2021-05-13
关键词EGFR ERBB2 gene fusions tyrosine kinase inhibitors young lung cancer patients
ISSN号0020-7136
DOI10.1002/ijc.33583
通讯作者Luo, Zhuang(luozhuang@ydyy.cn) ; Wang, Xuming(wangxuming@ydyy.cn) ; Cao, Yang(caoyang0342@gzucm.edu.cn)
英文摘要The aim of the study was to investigate age-dependent tendency of genomic alterations in lung cancer, and also to examine mutational profiles and its association with clinical treatment outcomes in young adenocarcinoma patients. By studying 7858 lung cancer samples using targeted-gene sequencing, we investigated genomic differences and clinical on-treatment time (OTT) to different therapies between young (<= 45 years) and old (> 45 years) patients. The age-dependent trend test for genomic alterations in all patients revealed steady increases in tumor mutation burden and alterations in a number of genes with age, including KRAS, MET, CDKN2A, PIK3CA and MDM2, while the frequencies of ALK, ROS1 and RET fusions and ERBB2 mutations were decreasing. The highest rate of EGFR alterations was observed in the 45 similar to 50 years age group. Comparisons of young and old adenocarcinoma patients found that young patients were characterized by a higher prevalence of ALK, ROS1 and RET fusions, and ERBB2 exon-20 insertions and EGFR exon-19 deletions. Actionable mutations were highly prevalent in young adenocarcinoma patients, with 88% of patients harboring at least one actionable genetic alteration. First-line therapies in EGFR-positive patients (n = 979) by EGFR tyrosine kinase inhibitors or chemotherapy resulted in similar OTT between young and old patients. Somatic interaction analyses implied that young EGFR-positive patients were more likely to also have PIK3CA, MET, TP53 and RB1 mutations than old patients. Lung cancer in young patients, and especially those with adenocarcinoma, exhibited different clinical features and genomic attributes compared to old patients, which should be considered for therapeutic decision-making purposes.
WOS关键词FUSION VARIANT ; EGFR ; RESISTANCE ; GEFITINIB ; CELLS ; ADENOCARCINOMA ; IDENTIFICATION ; DISCOVERY ; SURVIVAL ; GUIDANCE
资助项目National Natural Science Foundation of China[81871261]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000649834200001
出版者WILEY
资助机构National Natural Science Foundation of China
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/122460]  
专题中国科学院合肥物质科学研究院
通讯作者Luo, Zhuang; Wang, Xuming; Cao, Yang
作者单位1.Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing, Peoples R China
2.Geneseeq Technol Inc, Translat Med Res Inst, Toronto, ON, Canada
3.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510300, Guangdong, Peoples R China
4.Kunming Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Kunming 650032, Yunnan, Peoples R China
5.Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China
6.Nanjing Geneseeq Technol Inc, Med Dept, Nanjing, Jiangsu, Peoples R China
7.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Surg, Hangzhou, Zhejiang, Peoples R China
8.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Zhejiang, Peoples R China
推荐引用方式
GB/T 7714		 Cai, Lei,Chen, Yong,Tong, Xiaoling,et al. The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients[J]. INTERNATIONAL JOURNAL OF CANCER,2021.
APA Cai, Lei.,Chen, Yong.,Tong, Xiaoling.,Wu, Xue.,Bao, Hua.,...&Cao, Yang.(2021).The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients.INTERNATIONAL JOURNAL OF CANCER.
MLA Cai, Lei,et al."The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients".INTERNATIONAL JOURNAL OF CANCER (2021).

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来源：合肥物质科学研究院

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