Zhou Yangying, Xu Zhijie, Lin Wei, Duan Yumei, Lu Can, Liu Wei, Su Weiping, Yan Yuanliang, Liu Huan, Liu Li, Zhong Meizuo, Zhou Jianhua, Zhu Hong
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2019 Jul 25;9:683. doi: 10.3389/fonc.2019.00683. eCollection 2019.
Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in and , components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were (3/9; 33.3%), (3/9; 33.3%), (2/9; 22.2%), (2/9; 22.2%), (2/9; 22.2%), and (2/9; 22.2%) compared with (4/6; 66.7%), (3/6; 50.0%), (2/6; 33.3%), (2/6; 33.3%), and (2/6; 33.3%) in EBV-negative DLBCL. and alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.
爱泼斯坦-巴尔病毒（EBV）阳性弥漫性大B细胞淋巴瘤（EBV+ DLBCL）是一种罕见的淋巴瘤，在老年患者中发病率高、药物反应差且预后不良。尽管DLBCL在基因组分析和精准医学方面取得了进展，但EBV+ DLBCL的特征和了解仍然不足。我们纳入了236例DLBCL患者进行EBV编码mRNA（EBER）杂交检测，并通过下一代测序（NGS）分析了9例EBV+和6例EBV阴性病例。然后，我们对22例EBV+和30例EBV阴性病例进行了荧光杂交（FISH）和免疫组织化学（IHC），以分析染色体重排和基因表达。EBER结果显示阳性率为9.3%（22/236）。NGS结果揭示了凋亡和NF-κB途径的组成部分在 和 中存在反复改变。与EBV阴性DLBCL中的 （4/6；66.7%）、 （3/6；50.0%）、 （2/6；33.3%）、 （2/6；33.3%）和 （2/6；33.3%）相比，EBV+ DLBCL中最常发生突变的基因是 （3/9；33.3%）、 （3/9；33.3%）、 （2/9；22.2%）、 （2/9；22.2%）、 （2/9；22.2%）和 （2/9；22.2%）。 和 的改变是两组中突变差异最明显的基因。FISH检测显示EBV+队列中的重排率较低。此外，KMT2D表达在两个队列中均高表达且与不良生存相关。MYC仅在EBV+ DLBCL队列中过表达且与预后较差相关。总之，我们描绘了EBV+和EBV阴性DLBCL不同的突变谱，并验证了KMT2D和MYC的差异表达及其潜在的预后影响，从而为DLBCL的发病机制和精准医学提供了新的视角。
