AUTHOR=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 

TITLE=Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00683

DOI=10.3389/fonc.2019.00683

ISSN=2234-943X

ABSTRACT=<p>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) <italic>in situ</italic> hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence <italic>in situ</italic> 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 <italic>MYC</italic> and <italic>RHOA</italic>, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were <italic>MYC</italic> (3/9; 33.3%), <italic>RHOA</italic> (3/9; 33.3%), <italic>PIM1</italic> (2/9; 22.2%), <italic>MEF2B</italic> (2/9; 22.2%), <italic>MYD88</italic> (2/9; 22.2%), and <italic>CD79B</italic> (2/9; 22.2%) compared with <italic>KMT2D</italic> (4/6; 66.7%), <italic>CREBBP</italic> (3/6; 50.0%), <italic>PIM1</italic> (2/6; 33.3%), <italic>TNFAIP3</italic> (2/6; 33.3%), and <italic>BCL2</italic> (2/6; 33.3%) in EBV-negative DLBCL. <italic>MYC</italic> and <italic>KMT2D</italic> 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.</p>