TY - JOUR
T1 - Methylation status of the Epstein-Barr virus major latent promoter C in latrogenic B cell lymphoproliferative disease
T2 - Application of PCR-based analysis
AU - Qian, Tao
AU - Swinnen, Lode J.
AU - Yang, Jie
AU - Srivastava, Gopesh
AU - Robertson, Keith D.
AU - Ambinder, Richard F.
PY - 1999/8
Y1 - 1999/8
N2 - 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.
AB - 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.
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U2 - 10.1016/s0002-9440(10)65157-7
DO - 10.1016/s0002-9440(10)65157-7
M3 - Article
C2 - 10433954
AN - SCOPUS:0344980092
SN - 0002-9440
VL - 155
SP - 619
EP - 625
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -