基于全外显子组测序的胸腺癌基因组分析和生物标志物探索的回顾性队列研究  

Genomic analysis and biomarker discovery of thymic cancer based on whole exome sequencing:A retrospective cohort study

作　　者：向润[1] 谢少华 廖琼 李强[1] 邵伟康 李娟[4] XIANG Run;XIE Shaohua;LIAO Qiong;LI Qiang;SHAO Weikang;LI Juan(Department of Thoracic Surgery,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu,610041,P.R.China;Department of Pathology,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu,610041,P.R.China;Genecast Biotechnology Co.,Ltd.,Wuxi,214000,Jiangsu,P.R.China;Department of Medical Oncology,Sichuan Clinical Research Center for Cancer,Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China,Chengdu,610041,P.R.China)

机构地区：[1]四川省肿瘤临床医学研究中心,四川省肿瘤医院·研究所,四川省癌症防治中心,电子科技大学附属医院胸外科,成都610041 [2]四川省肿瘤临床医学研究中心,四川省肿瘤医院·研究所,四川省癌症防治中心,电子科技大学附属医院病理科,成都610041 [3]无锡臻和生物科技有限公司,江苏无锡214000 [4]四川省肿瘤临床医学研究中心,四川省肿瘤医院·研究所,四川省癌症防治中心,电子科技大学附属医院肿瘤内科,成都610041

出　　处：《中国胸心血管外科临床杂志》2024年第2期288-303,共16页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：目的检测胸腺癌(thymic carcinoma,TC)患者基因突变情况,以探索预后相关因素和治疗的潜在靶点。方法回顾性纳入四川省肿瘤医院2015年1月—2021年2月收治的TC患者。对TC患者肿瘤组织及其对照外周血样本进行全外显子组测序,并对原始数据进行生物信息学分析和统计学分析。结果最终纳入24例TC患者,其中男16例、女8例,中位年龄55(42~74)岁。TC患者单核苷酸突变频率最高的为TTN基因(42%)、HSPG2(29%)和OBSCN(29%)。发生染色体拷贝数变异频率较高的是ZNF276基因(54%,loss),BEND3(50%,loss),DHODH(50%,loss)和VAC14(50%,loss)。其中25%TC患者为微卫星不稳定(microsatellite instability,MSI)型,平均肿瘤突变负荷(tumor mutation burden,TMB)为9.86。结论此研究是迄今为止第一个关于中国TC患者基因突变情况的全面分析。TTN、OBSCN和ZNF276基因的突变频率较高,通过MSI、TMB等生物标志物分析,表明TC患者有从免疫治疗中获益的潜能。Objective To examined gene mutations in thymic carcinoma(TC)patients and to explore prognostic correlates and potential targets for therapy.Methods We retrospectively included TC patients in Sichuan Cancer Hospital between January 2015 and Febuary 2021.Whole-exome sequencing was performed on tumor tissues from TC patients and their control peripheral blood samples,and the raw data were subjected to bioinformatics analysis and statistical analysis.Results We finally included 24 TC patients with 16 males and 8 females at a median age of 55(42-74)years.The highest frequency of single nucleotide mutations in this cohort were in the TTN gene(42%),HSPG2(29%),and OBSCN(29%).Higher frequency of copy number variations occurred in ZNF276 gene(54%,loss),BEND3(50%,loss),DHODH(50%,loss),and VAC14(50%,loss).Microsatellite instability(MSI)phenotype was found in 25%of the patients,and the mean tumor mutation burden(TMB)was 9.86.Conclusion This study is the first comprehensive analysis of the mutation profile of thymic carcinoma in China to date.The mutation frequencies of TTN,OBSCN,and ZNF276 genes were high.The biomarker analysis suggests that patients may benefit from immunotherapy and have a long effective survival.

关 键 词：胸腺癌 基因突变 全外显子XEG测序 回顾性队列研究 

分 类 号：R736.3[医药卫生—肿瘤]