Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of T...Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.Methods:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017.Patient samples were sequenced using a 324-gene platform with licensed technologies.In this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and TNENs.Results:The mutational profiles between TCs and TNENs were diverse.The genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and TSC2.Prognostic analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN patients.Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)signaling.Conclusion:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.展开更多
目的探讨借鉴乳腺影像报告和数据系统(breast imaging reporting and data system,BI-RADS)分类方式对胸腺肿瘤MRI表现进行分类诊断的可行性。材料与方法纳入2014年5月至2018年8月MRI检查发现85例经病理证实的胸腺肿瘤,结合MRI信号和形...目的探讨借鉴乳腺影像报告和数据系统(breast imaging reporting and data system,BI-RADS)分类方式对胸腺肿瘤MRI表现进行分类诊断的可行性。材料与方法纳入2014年5月至2018年8月MRI检查发现85例经病理证实的胸腺肿瘤,结合MRI信号和形态学特征,借鉴乳腺BI-RADS分级模式,对病灶进行Ⅰ~Ⅴ类的分类诊断,并与WHO的组织细胞分类和Masaoka-Koga分期进行匹配对照。结果MRI分期与WHO分类和Masaoka-Koga分期可以形成较好的对应关系。根据病灶的信号和形态特征,85例胸腺肿瘤中,15/16例胸腺囊性病变被划分为Ⅱ类,对应良性病变;2/3例良性胸腺增生、4例A型、15/17例AB型、14/17例B1胸腺瘤被划分为Ⅲ类,对应低危病变;5/6例B2型和6例B3型胸腺瘤被划分为Ⅳ类,对应高危病变;9/11例胸腺癌被划分为Ⅴ类,对应侵袭性恶性病变。Spearmen相关系数为0.808,t=12.499,P<0.01。结论利用多模态MRI信息将胸腺肿瘤划分为Ⅰ~Ⅴ类,在一定程度上体现了WHO的组织学分型和Masaoka-Koga分期特征,有利于胸腺瘤的诊断治疗计划。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82272913)National Multi-disciplinary Treatment Project for Major Disease(No.2020NMDTP)+2 种基金Shanghai Sailing Program of Science and Technology Commission of Shanghai Municipality(No.20YF1428100)Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2021QN126)Shanghai Chest Hospital(No.2020YNJCM10)
文摘Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.Methods:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017.Patient samples were sequenced using a 324-gene platform with licensed technologies.In this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and TNENs.Results:The mutational profiles between TCs and TNENs were diverse.The genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and TSC2.Prognostic analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN patients.Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)signaling.Conclusion:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.
文摘目的探讨借鉴乳腺影像报告和数据系统(breast imaging reporting and data system,BI-RADS)分类方式对胸腺肿瘤MRI表现进行分类诊断的可行性。材料与方法纳入2014年5月至2018年8月MRI检查发现85例经病理证实的胸腺肿瘤,结合MRI信号和形态学特征,借鉴乳腺BI-RADS分级模式,对病灶进行Ⅰ~Ⅴ类的分类诊断,并与WHO的组织细胞分类和Masaoka-Koga分期进行匹配对照。结果MRI分期与WHO分类和Masaoka-Koga分期可以形成较好的对应关系。根据病灶的信号和形态特征,85例胸腺肿瘤中,15/16例胸腺囊性病变被划分为Ⅱ类,对应良性病变;2/3例良性胸腺增生、4例A型、15/17例AB型、14/17例B1胸腺瘤被划分为Ⅲ类,对应低危病变;5/6例B2型和6例B3型胸腺瘤被划分为Ⅳ类,对应高危病变;9/11例胸腺癌被划分为Ⅴ类,对应侵袭性恶性病变。Spearmen相关系数为0.808,t=12.499,P<0.01。结论利用多模态MRI信息将胸腺肿瘤划分为Ⅰ~Ⅴ类,在一定程度上体现了WHO的组织学分型和Masaoka-Koga分期特征,有利于胸腺瘤的诊断治疗计划。
