Genetic abnormalities assist in pathological diagnosis and EBVpositive cell density impact survival in Chinese angioimmunoblastic T-cell lymphoma patients

查看全文 作　　者：Yunfei [1]Shi;Haojie [2]Wang;Yanfei [3]Liu;Mengping [1]Long;Ning [3]Ding;Lan [3]Mi;Yumei [1]Lai;Lixin [1]Zhou;Xinting [1]Diao;Xianghong [1]Li;Weiping [3]Liu;Jun [3]Zhu 机构地区：[1]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pathology,Peking University Cancer Hospital&Institute,Beijing 100142,China;[2]Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China;[3]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Lymphoma,Peking University Cancer Hospital&Institute,Beijing 100142,China 出　　处：《Chinese Journal of Cancer Research》索引2023年第35卷第5期,共14页 基　　金：supported by“Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing”(No.HP2021-31-50302). 摘　　要：Objective:To explore the application of genetic abnormalities in the diagnosis of angioimmunoblastic T-cell lymphoma(AITL)and the reliable pathological prognostic factors.Methods:This study included 53 AITL cases,which were reviewed for morphological patterns,immunophenotypes,presence of Hodgkin and Reed-Sternberg(HRS)-like cells,and co-occurrence of B cell proliferation.The Epstein-Barr virus(EBV)-positive cells in tissues were counted,and cases were classified into“EBV encoded RNA(EBER)high-density”group if>50/HPF.Targeted exome sequencing was performed.Results:Mutation data can assist AITL diagnosis:1)with considerable HRS-like cells(20 cases):RHOA mutated in 14 cases(IDH2 co-mutated in 3 cases,4 cases with rare RHOA mutation),TET2 was mutated in 5 cases(1 case comutated with DNMT3A),and DNMT3A mutated in 1 case;2)accompanied with B cell lymphoma(7 cases):RHOA mutated in 4 cases(1 case had IDH2 mutation),TET2 mutated in 2 cases and DNMT3A mutated in 1 case;3)mimic peripheral T cell lymphoma,not otherwise specified(5 cases):RHOA mutated in 2 cases(IDH2 co-mutated in 1 case),TET2 mutated in 3 cases,and DNMT3A mutated in 1 case;4)pattern 1(1 case),RHOA and TET2 co-mutated.Besides RHOAG17V(30/35),rare variant included RHOAK18N,RHOAR68H,RHOAC83Y,RHOAD120G and RHOAG17del,IDH2R172 co-mutated with IDH2M397V in one case.There were recurrent mutations of FAT3,PCLO and PIEZO1 and genes of epigenetic remodeling,T-cell activation,APC and PI3K/AKT pathway.EBER high-density independently indicated adverse overall survival and progression-free survival(P=0.046 and P=0.008,KaplanMeier/log-rank).Conclusions:Over half AITL cases might be confused in diagnosis for certain conditions without mutation data.Targeted exome sequencing with a comprehensive panel is crucial to detect both hot-spot and rare mutation variants for RHOA and IDH2 and other recurrent mutated genes in addition to TET2 and DNMT3A.EBER highdensity independently indicated adverse survival. 关 键 词：T cell LYMPHOMA MUTATION PATHOLOGY PROGNOSIS