Cargando…
Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes
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 characteri...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669985/ https://www.ncbi.nlm.nih.gov/pubmed/31403034 http://dx.doi.org/10.3389/fonc.2019.00683 |
_version_ | 1783440481729904640 |
---|---|
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 |
author_facet | 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 |
author_sort | Zhou, Yangying |
collection | PubMed |
description | 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-κB 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. |
format | Online Article Text |
id | pubmed-6669985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66699852019-08-09 Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes 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 Front Oncol Oncology 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-κB 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. Frontiers Media S.A. 2019-07-25 /pmc/articles/PMC6669985/ /pubmed/31403034 http://dx.doi.org/10.3389/fonc.2019.00683 Text en Copyright © 2019 Zhou, Xu, Lin, Duan, Lu, Liu, Su, Yan, Liu, Liu, Zhong, Zhou and Zhu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology 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 Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title | Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title_full | Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title_fullStr | Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title_full_unstemmed | Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title_short | Comprehensive Genomic Profiling of EBV-Positive Diffuse Large B-cell Lymphoma and the Expression and Clinicopathological Correlations of Some Related Genes |
title_sort | comprehensive genomic profiling of ebv-positive diffuse large b-cell lymphoma and the expression and clinicopathological correlations of some related genes |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669985/ https://www.ncbi.nlm.nih.gov/pubmed/31403034 http://dx.doi.org/10.3389/fonc.2019.00683 |
work_keys_str_mv | AT zhouyangying comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT xuzhijie comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT linwei comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT duanyumei comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT lucan comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT liuwei comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT suweiping comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT yanyuanliang comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT liuhuan comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT liuli comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT zhongmeizuo comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT zhoujianhua comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes AT zhuhong comprehensivegenomicprofilingofebvpositivediffuselargebcelllymphomaandtheexpressionandclinicopathologicalcorrelationsofsomerelatedgenes |