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

doi:10.1002/ijc.33583

	The genomic landscape of young and old lung cancer patients highlights age-dependent mutation frequencies and clinical actionability in young patients
	Cai, Lei 4,6; Chen, Yong 5; Tong, Xiaoling 7; Wu, Xue 7; Bao, Hua 7; Shao, Yang 1,8; Luo, Zhuang 2; Wang, Xuming 2; Cao, Yang 3
刊名	INTERNATIONAL JOURNAL OF CANCER
	2021-05-13
关键词	EGFR ERBB2 gene fusions tyrosine kinase inhibitors young lung cancer patients
ISSN号	0020-7136
DOI	10.1002/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.
资助项目	National Natural Science Foundation of China[81871261]
WOS关键词	FUSION VARIANT ; EGFR ; RESISTANCE ; GEFITINIB ; CELLS ; ADENOCARCINOMA ; IDENTIFICATION ; DISCOVERY ; SURVIVAL ; GUIDANCE
WOS研究方向	Oncology
语种	英语
出版者	WILEY
WOS记录号	WOS:000649834200001
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
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.Nanjing Geneseeq Technol Inc, Med Dept, Nanjing, Jiangsu, Peoples R China 2.Kunming Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Kunming 650032, Yunnan, Peoples R China 3.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510300, Guangdong, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Surg, Hangzhou, Zhejiang, Peoples R China 5.Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing, Peoples R China 6.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Zhejiang, Peoples R China 7.Geneseeq Technol Inc, Translat Med Res Inst, Toronto, ON, Canada 8.Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, 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).