Epstein-Barr virus DNA and latent gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas.

Epstein-Barr virus (EBV)-specific DNA sequences were detected by polymerase chain reaction analysis in 15 of 47 (32%) DNA extracts prepared from CD30-positive (Ki-1 antigen-positive) anaplastic large cell (ALC) lymphomas. EBV-encoded RNA (EBER) transcripts could be detected by in situ hybridization in the tumor cells of 9 of 11 EBV DNA-positive cases. Twenty-eight cases were examined by immunohistology on cryostat sections for the presence of the EBV-encoded latent membrane protein (LMP), the nuclear antigen 2 (EBNA2), the BZLF1 transactivator protein, and the late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in lymphoma cells of five cases (18%); two of these cases additionally expressed EBNA2. BZLF1 protein and gp350/250 immunoreactivity was absent in all instances. All LMP-positive cases contained EBV DNA and EBER sequences. The pattern of EBV latent protein expression in ALC lymphomas showed heterogeneity with respect to EBNA2 expression: LMP-positive/EBNA2-negative cases displayed a pattern previously described for undifferentiated nasopharyngeal carcinomas and Hodgkin's disease, whereas LMP-positive and EBNA2-positive cases showed parallels to lymphoblastoid cell lines. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiologic role for EBV in a proportion of CD30-positive ALC lymphomas.

[1]  G. Packham,et al.  Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia , 1991, Journal of virology.

[2]  S. Hamilton-Dutoit,et al.  Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease , 1991, The Lancet.

[3]  L. Young,et al.  Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man , 1991, The Journal of experimental medicine.

[4]  L. P. Dehner Ki-1 lymphoma. , 1991, Pediatric pathology.

[5]  M. Sauter,et al.  Flow cytometric analysis of Epstein-Barr virus (EBV) latent membrane protein expression in EBV-infected Raji cells. , 1990, The Journal of general virology.

[6]  H. Stein,et al.  High incidence of Epstein-Barr virus genomes in Hodgkin's disease. , 1990, The American journal of pathology.

[7]  E. Kieff,et al.  Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1 , 1990, Journal of virology.

[8]  G. Klein,et al.  Morphological transformation of human keratinocytes expressing the LMP gene of Epstein Barr virus , 1990, Nature.

[9]  E. Kieff,et al.  Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23 , 1990, Journal of virology.

[10]  L. Young,et al.  Epstein–Barr virus latent membrane protein inhibits human epithelial cell differentiation , 1990, Nature.

[11]  R. Warnke,et al.  CD30‐positive large cell lymphomas (‘Ki‐1 lymphoma’) are associated with a chromosomal translocation involving 5q35 , 1990, British journal of haematology.

[12]  E. Kieff,et al.  Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. , 1989, The New England journal of medicine.

[13]  H. Stein,et al.  Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. , 1989, Blood.

[14]  H. Stein,et al.  In situ hybridization for procollagen types I, III and IV mRNA in normal and fibrotic rat liver: Evidence for predominant expression in nonparenchymal liver cells , 1989, Hepatology.

[15]  R. Warnke,et al.  Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease. , 1989, The New England journal of medicine.

[16]  E. Kieff,et al.  Epstein-Barr virus latent infection membrane protein alters the human B-lymphocyte phenotype: deletion of the amino terminus abolishes activity , 1988, Journal of virology.

[17]  Pierre Busson,et al.  Expression of Epstein‐Barr virus‐encoded proteins in nasopharyngeal carcinoma , 1988, International journal of cancer.

[18]  S. Burrows,et al.  Cytotoxic T-cell clones discriminate between A- and B-type Epstein-Barr virus transformants , 1988, Nature.

[19]  L. Young,et al.  Differences in B cell growth phenotype reflect novel patterns of Epstein‐Barr virus latent gene expression in Burkitt's lymphoma cells. , 1987, The EMBO journal.

[20]  T. Iftner,et al.  Enhancement of Epstein-Barr virus membrane protein (LMP) expression by serum, TPA, or n-butyrate in latently infected Raji cells. , 1987, Virology.

[21]  E. Kieff,et al.  Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells. , 1987, The Journal of general virology.

[22]  J. Steitz,et al.  Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Kieff,et al.  An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells , 1985, Cell.

[24]  K. Lennert,et al.  The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. , 1985, Blood.

[25]  G. Lenoir,et al.  Identification of the coding region for a second Epstein‐Barr virus nuclear antigen (EBNA 2) by transfection of cloned DNA fragments. , 1985, The EMBO journal.

[26]  A. Polack,et al.  A complete set of overlapping cosmid clones of M-ABA virus derived from nasopharyngeal carcinoma and its similarity to other Epstein-Barr virus isolates. , 1984, Gene.

[27]  Johannes Gerdes,et al.  Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation , 1983, International journal of cancer.

[28]  J. Arrand,et al.  In vitro transcription of two Epstein-Barr virus specified small RNA molecules. , 1982, Nucleic acids research.