Gene Expression Profiling of Epstein-Barr Virus-positive and -negative Monomorphic B-cell Posttransplant Lymphoproliferative DisordersCraig, Fiona E. MD*; Johnson, Lawrence R. MD*; Harvey, Stephen A. K. PhD†; Nalesnik, Michael A. MD‡; Luo, Jianhua H. MD, PhD§; Bhattacharya, Soumyaroop D. MS∥; Swerdlow, Steven H. MD*Author Information *Division of Hematopathology, Department of Pathology †Department of Ophthalmology ‡Division of Transplantation and Hepatic Pathology, Department of Pathology §Division of Molecular Diagnostics, Department of Pathology ∥Center for Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA Supported in part by NIH grant no. PO1 CA47445. Portions of this work were presented as a poster at the 2005 USCAP Meeting, San Antonio. Reprints: Dr Fiona E. Craig, MD, 200 Lothrop Street, PUH C606, Pittsburgh, PA 15213 (e-mail: firstname.lastname@example.org). Diagnostic Molecular Pathology: September 2007 - Volume 16 - Issue 3 - pp 158-168 doi: 10.1097/PDM.0b013e31804f54a9 Buy Metrics Abstract Although most posttransplant lymphoproliferative disorders (PTLD) are related to Epstein-Barr virus (EBV) infection, approximately 20% lack detectable EBV (EBV−). It is uncertain whether the latter cases are truly distinct from EBV+ PTLD or possibly relate to another infectious agent. This study used gene expression profiling to further investigate the relationship between EBV+ and EBV− monomorphic B-cell PTLD, and to search for clues to their pathogenesis. Affymetrix HU133A GeneChips were used to compare 4 EBV+ and 4 EBV− cases of monomorphic B-cell PTLD. Hierarchical clustering successfully distinguished the EBV+ and EBV− groups. Relative to EBV− PTLD, 54 transcripts were over-expressed in EBV+ PTLD. The transcripts identified included IRF7 (a known regulator of EBV LMP1 expression), EBI2 (EBV-induced gene 2), and 3 that are interferon induced (MX1, IFITM1, and IFITM3). In addition, the EBV+ group contained 232 transcripts decreased relative to the EBV− group, including changes concordant with those previously reported after EBV infection of cultured B-cell lines. In summary, in a small group of monomorphic B-cell PTLD, EBV+ cases demonstrated a subset of gene expression changes associated with EBV infection of B cells. By contrast, EBV− PTLD lacked viral-associated changes suggesting that they are biologically distinct. © 2007 Lippincott Williams & Wilkins, Inc.