Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease

D. F. Patton, C. W. Wilkowski, C. A. Hanson, R. Shapiro, K. J. Gajl-Peczalska, A. H. Filipovich, K. L. McClain

Research output: Contribution to journalArticle

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Abstract

Analysis of the genomic termini of Epstein-Barr virus can provide valuable insight into the cofactor role of EBV in the development of B cell lymphomas and lympoproliferative disease. We report EBV genomic findings in pathologic specimens from 10 patients who developed lymphoma or lymphoproliferative disease after renal or bone marrow transplantation. Endonuclease restriction patterns of EBV genomic termini are highly variable in size in both the episomal and linear configuration. This variability in fragment size permits direct assessment of tissue clonality in EBV-infected material. Hybridization with terminus-specific probes also reveals configuration of viral genome (circular and latent vs. linear and replicative). Nine of 10 patients had tumors with mono- or biclonal episomal markers, and 4 of 10 had evidence of linear or replicative virus. Analyses of virally determined markers were compared to immunoglobulin gene rearrangement studies, histologic immunophenotyping, cytogenetics, and clinical outcome. These 10 cases represent a spectrum of lymphoproliferative disorders ranging from benign polyclonal to malignant monoclonal disease. The molecular data lend credence to two important aspects of viral pathogenesis: (1) the finding of a homogeneous episomal population in the monoclonal tumors suggests that EBV infection is an early event in tumorigenesis that occurs before clonal expansion; and (2) therapeutic efficacy of acyclovir has been shown only in presence of polyclonal disease but may impact on intermediate stages where linear replicative virus can be found. Finally, the various assessments of tumor clonality were compared, and although heterogeneity was seen among patients and among diagnostic methods, analyses at the molecular level using virus and immunoglobulin gene specific probes were concurrent and provide the more sensitive means for detection of clonality.

Original languageEnglish (US)
Pages (from-to)1080-1084
Number of pages5
JournalTransplantation
Volume49
Issue number6
StatePublished - 1990
Externally publishedYes

Fingerprint

Human Herpesvirus 4
Immunoglobulin Genes
Viruses
Immunophenotyping
Neoplasms
Epstein-Barr Virus Infections
Lymphoproliferative Disorders
Acyclovir
Gene Rearrangement
Viral Genome
DNA Restriction Enzymes
B-Cell Lymphoma
Bone Marrow Transplantation
Cytogenetics
Lymphoma
Carcinogenesis
Kidney
Population
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Transplantation

Cite this

Patton, D. F., Wilkowski, C. W., Hanson, C. A., Shapiro, R., Gajl-Peczalska, K. J., Filipovich, A. H., & McClain, K. L. (1990). Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease. Transplantation, 49(6), 1080-1084.

Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease. / Patton, D. F.; Wilkowski, C. W.; Hanson, C. A.; Shapiro, R.; Gajl-Peczalska, K. J.; Filipovich, A. H.; McClain, K. L.

In: Transplantation, Vol. 49, No. 6, 1990, p. 1080-1084.

Research output: Contribution to journalArticle

Patton, DF, Wilkowski, CW, Hanson, CA, Shapiro, R, Gajl-Peczalska, KJ, Filipovich, AH & McClain, KL 1990, 'Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease', Transplantation, vol. 49, no. 6, pp. 1080-1084.
Patton DF, Wilkowski CW, Hanson CA, Shapiro R, Gajl-Peczalska KJ, Filipovich AH et al. Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease. Transplantation. 1990;49(6):1080-1084.
Patton, D. F. ; Wilkowski, C. W. ; Hanson, C. A. ; Shapiro, R. ; Gajl-Peczalska, K. J. ; Filipovich, A. H. ; McClain, K. L. / Epstein-Barr virus-determined clonality in posttransplant lymphoproliferative disease. In: Transplantation. 1990 ; Vol. 49, No. 6. pp. 1080-1084.
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