PMID- 31403034 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231013 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 9 DP - 2019 TI - Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes. PG - 683 LID - 10.3389/fonc.2019.00683 [doi] LID - 683 AB - 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) in situ hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence in situ 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 MYC and RHOA, components of apoptosis and NF-kappaB pathways. The most frequently mutated genes in EBV+ DLBCL were MYC (3/9; 33.3%), RHOA (3/9; 33.3%), PIM1 (2/9; 22.2%), MEF2B (2/9; 22.2%), MYD88 (2/9; 22.2%), and CD79B (2/9; 22.2%) compared with KMT2D (4/6; 66.7%), CREBBP (3/6; 50.0%), PIM1 (2/6; 33.3%), TNFAIP3 (2/6; 33.3%), and BCL2 (2/6; 33.3%) in EBV-negative DLBCL. MYC and KMT2D 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. FAU - Zhou, Yangying AU - Zhou Y AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. FAU - Xu, Zhijie AU - Xu Z AD - Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. FAU - Lin, Wei AU - Lin W AD - Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. FAU - Duan, Yumei AU - Duan Y AD - Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. FAU - Lu, Can AU - Lu C AD - Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. FAU - Liu, Wei AU - Liu W AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. FAU - Su, Weiping AU - Su W AD - Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China. FAU - Yan, Yuanliang AU - Yan Y AD - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China. FAU - Liu, Huan AU - Liu H AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. FAU - Liu, Li AU - Liu L AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. FAU - Zhong, Meizuo AU - Zhong M AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. FAU - Zhou, Jianhua AU - Zhou J AD - Department of Pathology, Xiangya Hospital, Central South University, Changsha, China. FAU - Zhu, Hong AU - Zhu H AD - Department of Oncology, Xiangya Hospital, Central South University, Changsha, China. LA - eng PT - Journal Article DEP - 20190725 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC6669985 OTO - NOTNLM OT - EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) OT - KMT2D OT - MYC OT - fluorescence in situ hybridizations OT - immunohistochemistry OT - next-generation sequencing EDAT- 2019/08/14 06:00 MHDA- 2019/08/14 06:01 PMCR- 2019/01/01 CRDT- 2019/08/13 06:00 PHST- 2019/05/07 00:00 [received] PHST- 2019/07/10 00:00 [accepted] PHST- 2019/08/13 06:00 [entrez] PHST- 2019/08/14 06:00 [pubmed] PHST- 2019/08/14 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2019.00683 [doi] PST - epublish SO - Front Oncol. 2019 Jul 25;9:683. doi: 10.3389/fonc.2019.00683. eCollection 2019.