Spectrum of EGFR aberrations and potential clinical implications:insights from integrative pan-cancer analysis  

作　　者：Haijing Liu Bo Zhang Zhifu Sun 

机构地区：[1]Department of Pathology,School of Basic Medical Sciences,Third Hospital,Peking University Health Science Center,Beijing,100191,P.R.China [2]Division of Biomedical Statistics and Informatics,Department of Health Sciences Research,Mayo Clinic,Rochester,MN,55905,USA

出　　处：《Cancer Communications》2020年第1期43-59,共17页癌症通讯（英文）

基　　金：China Scholarship Council,Grant/Award Number:201806015028;Chinese National Natural Science Foundation,Grant/Award Numbers:81101998,81872018,81372292;Chinese Ministry of Science and Technology,Grant/Award Number:2017YFC0110200;Mayo Clinic Center for Individualized Medicine。

摘　　要：Background:Human epidermal growth factor receptor(EGFR)is an oncogenic gene and one of top targets of precision therapy in lung cancer with EGFR mutations.Although there are many reports for some individual cancers,comprehensive profiling of EGFR mutations,overexpression,amplification,DNA methylation,and their clinical associations across many different cancers simultaneously was not available.This study aimed to fill the gap and provide insights to the alteration spectrum of EGFR and its therapeutic and prognostic implications.Methods:The Cancer Genome Atlas(TCGA)datasets for 32 cancer types involving 11,314 patients were analyzed for alterations(mutations and amplification/deletion),abnormal expression and DNA methylation in EGFR gene.Mutation frequency,genomic location distribution,functional impact,and clinical targeted therapy implication were compared among different cancer types,and their associations with patient survival were analyzed.Results:EGFR alteration frequency,mutation sites across functional domains,amplification,overexpression,and DNA methylation patterns differed greatly among different cancer types.The overall mutation frequency in all cancers combined was relatively low.Targetable mutations,mainly in lung cancer,were primarily found in the Pkinase_Tyr domain.Glioblastoma multiforme had the highest rate of alterations,but it was dominated by gene amplification and most mutations were in the Furin-like domain where targeted therapy was less effective.Low-grade glioma often had gene amplification and increased EGFR expression which was associated with poor outcome.Colon and pancreatic adenocarcinoma had very few EGFR mutations;however,high EGFR expression was significantly associated with short patient survival.Squamous cell carcinoma regardless of their sites(the head and neck,lung,or esophagus)exhibited similar characteristics with an alteration frequency of about 5.0%,was dominated by gene amplification,and had increased EGFR expression generally associated with short patient survival.DNA me

关 键 词：EGFR expression EGFR mutation epidermal growth factor receptor pan-cancer profiling patient survival targeted therapy The Cancer Genome Atlas(TCGA) 

分 类 号：R73[医药卫生—肿瘤]