遗传异常有助于病理诊断，ebv阳性细胞密度影响中国血管免疫母细胞淋巴瘤患者的生存。

IF 7 2区医学 Q1 ONCOLOGY

Chinese Journal of Cancer Research Pub Date : 2023-10-30 DOI:10.21147/j.issn.1000-9604.2023.05.10

Yunfei Shi, Haojie Wang, Yanfei Liu, Mengping Long, Ning Ding, Lan Mi, Yumei Lai, Lixin Zhou, Xinting Diao, Xianghong Li, Weiping Liu, Jun Zhu

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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 co-mutated 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. 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引用次数: 0

摘要

目的:探讨遗传异常在血管免疫母细胞性t细胞淋巴瘤(AITL)诊断中的应用及可靠的病理预后因素。方法:对53例AITL患者的形态学、免疫表型、HRS样细胞的存在及B细胞增殖的共现情况进行回顾性分析。统计组织中eb病毒(EBV)阳性细胞数，将>50/HPF归为“EBV编码RNA (EBER)高密度”组。进行靶向外显子组测序。结果:突变资料可辅助AITL诊断:1)有相当数量的hrs样细胞(20例):RHOA突变14例(IDH2共突变3例，RHOA罕见突变4例)，TET2突变5例(与DNMT3A共突变1例)，DNMT3A突变1例;2)伴有B细胞淋巴瘤(7例):RHOA突变4例(1例伴有IDH2突变)，TET2突变2例，DNMT3A突变1例;3)模拟外周T细胞淋巴瘤，无其他特异性(5例):RHOA突变2例(IDH2共突变1例)，TET2突变3例，DNMT3A突变1例;4)模式1(1例)，RHOA与TET2共突变。除RHOAG17V(30/35)外，罕见变异包括RHOAK18N、RHOAR68H、RHOAC83Y、RHOAD120G和RHOAG17del, IDH2R172与IDH2M397V共突变1例。FAT3、PCLO、PIEZO1及表观遗传重塑、t细胞活化、APC、PI3K/AKT通路基因反复突变。EBER高密度独立显示不良的总生存期和无进展生存期(P=0.046和P=0.008, Kaplan-Meier/log-rank)。结论:超过半数的AITL病例在没有突变数据的情况下可能会对某些情况的诊断产生混淆。综合面板的靶向外显子组测序对于检测RHOA和IDH2以及除TET2和DNMT3A外的其他复发突变基因的热点和罕见突变变体至关重要。EBER高密度独立提示生存不良。

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

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 co-mutated 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 RHOA^G17V (30/35), rare variant included RHOA^K18N, RHOA^R68H, RHOA^C83Y, RHOA^D120G and RHOA^G17del, IDH2^R172 co-mutated with IDH2^M397V 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, Kaplan-Meier/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 high-density independently indicated adverse survival.

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来源期刊

Chinese Journal of Cancer Research 医学-肿瘤学

自引率

9.80%

发文量

1726

审稿时长

4.5 months

期刊介绍： Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.