Genomic profiling of colorectal cancer in large-scale Chinese patients:amplification and somatic mutations in ERBB2  

作　　者：YUZHI LIU EVELYNE BISCHOF ZHIQIN CHEN JIAHUAN ZHOU BEI ZHANG DING ZHANG YONG GAO MING QUAN 

机构地区：[1]Department of Oncology,Shanghai East Hospital,Tongji University School of Medicine,Shanghai,China [2]State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Department of Oncology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China [3]Jiangsu Hengrui Pharmaceuticals Co.,Ltd.,Shanghai,China [4]D Medicines Inc.,Shanghai,China

出　　处：《Oncology Research》2024年第9期1429-1438,共10页肿瘤学研究（英文）

基　　金：sponsored by National Natural Science Foundation of China(Grant Numbers 81972280,81972290);Natural Science Foundation of Shanghai(Grant Number 23ZR1452300);Research Grant for Health Science and Technology of Pudong Health Bureau of Shanghai(Grant Number PW2022E-02);Academic Leaders Training Program of Pudong Health Bureau of Shanghai(Grant Number PWRd2022-02);Foundation of Beijing CSCO Clinical Oncology Research(Grant Number Y-HR2019-0384).

摘　　要：Objectives:Human epidermal growth factor receptor 2(HER2)-targeted therapies have demonstrated potential benefits for metastatic colorectal cancer(mCRC)patients with HER2 amplification,but are not satisfactory in cases of HER2 mutant CRCs.Methods:Consequently,further elucidation of amplifications and somatic mutations in erythroblastic oncogene B-2(ERBB2)is imperative.Comprehensive genomic profiling was conducted on 2454 Chinese CRC cases to evaluate genomic alterations in 733 cancer-related genes,tumor mutational burden,microsatellite instability,and programmed death ligand 1(PD-L1)expression.Results:Among 2454 CRC patients,85 cases(3.46%)exhibited ERBB2 amplification,and 55 cases(2.24%)carried ERBB2 mutation.p.R678Q(28%),p.V8421(24%),and p.S310F/Y(12%)were the most prevalent of the 16 detected mutation sites.In comparison to the ERBB2 altered(alt)group,KRAS/BRAF mutations were more prevalent in ERBB2 wild-type(wt)samples(ERBB2wt vs.ERBB2alt,KRAS:50.9%vs.25.6%,p<0.05;BRAF:8.5%vs.2.3%,p<0.05).32.7%(18/55)of CRCs with ERBB2 mutation exhibited microsatellite instability high(MSI-H),while no cases with HER2 amplification displayed MSI-H.Mutant genes varied between ERBB2 copy number variation(CNV)and ERBB2 single nucleotide variant(SNV);TP53 alterations tended to co-occur with ERBB2 amplification(92.3%)as opposed to ERBB2 mutation(58.3%).KRAS and PIK3CA alterations were more prevalent in ERBB2 SNV cases(KRAS/PIK3CA:45.8%/31.2%)compared to ERBB2 amplification cases(KRAS/PIK3CA:14.1%/7.7%).Conclusion:Our study delineates the landscape of HER2 alterations in a large-scale cohort of CRC patients from China.These findings enhance our understanding of the molecular features of Chinese CRC patients and offer valuable implications for further investigation.

关 键 词：Colorectal cancer ERBB2 HER2 Human epidermal growth factor receptor 2 Genetic profiling Precision oncology 

分 类 号：R735.3[医药卫生—肿瘤]