Methylation status of the Epstein-Barr virus major latent promoter C in latrogenic B cell lymphoproliferative disease: Application of PCR-based analysis

Tao Qian, Lode J. Swinnen, Jie Yang, Gopesh Srivastava, Keith D Robertson, Richard F. Ambinder

Research output: Contribution to journalArticle

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Abstract

The Epstein-Barr virus (EBV) major latent promoter C drives the expression of viral nuclear proteins important in lymphocyte immortalization and as targets for immune surveillance by cytotoxic T cells. Hypermethylation of the C promoter silences its transcription. This promoter is methylated and silent in Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma, and nasal lymphoma. However, it is never methylated in the EBV-immortalized lymphoblastoid cell lines that serve as a model for EBV-associated lymphoproliferative disease. We have analyzed C promoter methylation in iatrogenic EBV-associated B-cell lymphoproliferative disease, mainly posttransplant lymphoma, using a sensitive polymerase chain reaction-based C promoter methylation assay. Our results showed heterogeneity in lymphoproliferative disease with methylation of vital DNA in specimens from 3 of 13 patients. In specimens from two of these patients, only methylated viral DNA was detected and vital nuclear antigen expression was correspondingly restricted. Heterogeneity in C promoter methylation and expression of associated transcripts may be an important determinant of the growth properties of lymphoproliferative lesions and may provide an explanation for the failure of some tumors to respond to withdrawal or reduction of immunosuppressive therapy.

Original languageEnglish (US)
Pages (from-to)619-625
Number of pages7
JournalAmerican Journal of Pathology
Volume155
Issue number2
StatePublished - Aug 1999
Externally publishedYes

Fingerprint

Human Herpesvirus 4
Methylation
B-Lymphocytes
Polymerase Chain Reaction
Lymphoma
Nuclear Antigens
Burkitt Lymphoma
Viral DNA
Viral Proteins
DNA Methylation
Immunosuppressive Agents
Nuclear Proteins
Hodgkin Disease
Nose
Lymphocytes
T-Lymphocytes
Cell Line
Growth
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Methylation status of the Epstein-Barr virus major latent promoter C in latrogenic B cell lymphoproliferative disease : Application of PCR-based analysis. / Qian, Tao; Swinnen, Lode J.; Yang, Jie; Srivastava, Gopesh; Robertson, Keith D; Ambinder, Richard F.

In: American Journal of Pathology, Vol. 155, No. 2, 08.1999, p. 619-625.

Research output: Contribution to journalArticle

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AU - Srivastava, Gopesh

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AU - Ambinder, Richard F.

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