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

作者全名："Cai, Lei; Chen, Yong; Tong, Xiaoling; Wu, Xue; Bao, Hua; Shao, Yang; Luo, Zhuang; Wang, Xuming; Cao, Yang"

作者地址："[Cai, Lei] Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Thorac Surg, Hangzhou, Zhejiang, Peoples R China; [Cai, Lei] Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Zhejiang, Peoples R China; [Chen, Yong] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Tong, Xiaoling; Wu, Xue; Bao, Hua] Geneseeq Technol Inc, Translat Med Res Inst, Toronto, ON, Canada; [Shao, Yang] Nanjing Geneseeq Technol Inc, Med Dept, Nanjing, Jiangsu, Peoples R China; [Shao, Yang] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China; [Luo, Zhuang; Wang, Xuming] Kunming Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Kunming 650032, Yunnan, Peoples R China; [Cao, Yang] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510300, Guangdong, Peoples R China"

通信作者："Luo, Z; Wang, XM (corresponding author), Kunming Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Kunming 650032, Yunnan, Peoples R China.; Cao, Y (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510300, Guangdong, Peoples R China."

来源：INTERNATIONAL JOURNAL OF CANCER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000649834200001

JCR分区：Q1

影响因子：6.4

年份：2021

卷号：149

期号：4

开始页：883

结束页：892

文献类型：Article

关键词：EGFR; ERBB2; gene fusions; tyrosine kinase inhibitors; young lung cancer patients

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."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81871261]

基金资助正文：The work is supported by the National Natural Science Foundation of China (No.81871261).