Integrated copy number and gene expression profiling analysis of epstein-barr virus-positive diffuse large b-cell lymphoma

Heejei Yoon, Sanghui Park, Hyunjeong Ju, Sang Yun Ha, Insuk Sohn, Jisuk Jo, In Gu Do, Sookee Min, Seok Jin Kim, Won Seog Kim, Hae Yong Yoo, Young Hyeh Ko

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Viral oncogenes and host immunosenescence have been suggested as causes of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly. To investigate the molecular genetic basis of immune evasion and tumor outgrowth, we analyzed copy number alterations (CNAs) and gene expression profiles in EBV+DLBCL samples compared with EBV-DLBCL. There were relatively few genomic alterations in EBV+DLBCL compared with those detected in EBV-negative DLBCL. The most frequent CNAs (>30%) in EBV+DLBCLs were gains at 1q23.2-23.3, 1q23.3, 1q32.1, 5p15.3, 8q22.3, 8q24.1-24.2, and 9p24.1; losses at 6q27, 7q11.2, and 7q36.2-36.3 were also recurrent. A gene expression profile analysis identified the host immune response as a key molecular signature in EBV+DLBCL. Antiviral response genes, proinflammatory cytokines, and chemokines associated with the innate immune response were overexpressed, indicating the presence of a virusinduced inflammatory microenvironment. Genes associated with the B-cell receptor signaling pathway were downregulated. An integrated analysis indicated that SLAMF1 and PDL2 were key targets of the gains detected at 1q23.2-23.3 and 9p24.1. The chromosomal gain at 9p24.1 was associated with poor overall survival. Taken together, our results led to the identification of recurrent copy number alterations and distinct gene expression associated with the host immune response in EBV+DLBCL. We suggest that the upregulation of PDL2 on 9p24.1 promotes immune evasion and is associated with poor prognosis in EBV+DLBCL.

Original languageEnglish
Pages (from-to)383-396
Number of pages14
JournalGenes Chromosomes and Cancer
Volume54
Issue number6
DOIs
StatePublished - 1 Jun 2015

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