Molecular characterization of HHV-8 positive primary effusion lymphoma reveals pathogenetic and histogenetic features of the disease

Gianluca Gaidano, Daniela Capello, Lucia Fassone, Annunziata Gloghini, Anna Maria Cilia, Cristiano Ariatti, Daniela Buonaiuto, Daniela Vivenza, Margherita Gallicchio, Gian Carlo Avanzi, Maria Prat, Antonino Carbone

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Abstract

Background: Primary effusion lymphoma (PEL) associates with HHV-8 infection, preferentially develops in immunodeficient patients and grows in the serous body cavities. PEL derives from post-germinal center, pre-terminally differentiated B-cells. The pathogenesis of PEL is unclear and the sole identified genetic lesions are human herpesvirus type-8 (HHV-8) infection in all cases and EBV infection in 70% of cases. Epstein-Barr virus (EBV) infection in PEL displays a latency I phenotype. Objectives: To clarify the pathogenesis and histogenesis of PEL by investigating (1) the lymphoma karyotype; (2) the expression status of the Met tyrosine kinase receptor and of its ligand hepatocyte growth factor (HGF); (3) the molecular profile of EBV, with particular focus on mutations of EBNA-1 genes, which are thought to affect viral tumorigenicity in EBV-infected neoplasms displaying the latency I phenotype. Study design: Twenty-four PEL (nine cell lines and 15 primary specimens) formed the basis of the study. Karyotypes were investigated by conventional cytogenetics and fluorescent in situ hybridization (FISH) in selected cases. The expression status of Met and HGF was defined by multiple techniques, including RT-PCR, FACS analysis, immunocytochemistry, Western blot studies and ELISA. The molecular profile of EBNA-1 genes of EBV were investigated by DNA direct sequencing. Results: Trisomy 7, trisomy 12 and breaks at 1q21-q25 are recurrently associated with PEL. PEL consistently co-express Met and HGF both at the mRNA and protein level. Among aggressive B-cell lymphomas, Met/HGF co-expression appears to be relatively specific for PEL. The EBNA-1 gene of EBV displays a high degree of genetic heterogeneity in PEL, with no preferential association with one specific variant. Conclusions: PEL associates with recurrent chromosomal alterations, suggesting that viral infection is not sufficient for tumor development and that lesions of cellular genes may be required. The expression of Met/HGF by PEL cells may bear implications for the lymphoma proliferation and growth pattern, since Met/HGF interactions influence cell mitogenesis and motogenesis. EBV infection in PEL displays a latency I phenotype and fails to associate with specific EBNA-1 variants, suggesting that the role of EBV in PEL is not mediated by the major transforming pathways currently known in EBV positive lymphomas. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalJournal of Clinical Virology
Volume16
Issue number3
DOIs
Publication statusPublished - May 2000

Fingerprint

Primary Effusion Lymphoma
Human Herpesvirus 8
Hepatocyte Growth Factor
Human Herpesvirus 4
Epstein-Barr Virus Infections
Herpesviridae Infections
Lymphoma
Trisomy
Phenotype
Karyotype
Genes
Germinal Center
Genetic Heterogeneity
Receptor Protein-Tyrosine Kinases
B-Cell Lymphoma
Virus Diseases

Keywords

  • EBV
  • HGF
  • HHV-8
  • MET
  • Pathogenesis
  • Primary effusion lymphoma

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Virology
  • Immunology and Allergy
  • Infectious Diseases

Cite this

Molecular characterization of HHV-8 positive primary effusion lymphoma reveals pathogenetic and histogenetic features of the disease. / Gaidano, Gianluca; Capello, Daniela; Fassone, Lucia; Gloghini, Annunziata; Cilia, Anna Maria; Ariatti, Cristiano; Buonaiuto, Daniela; Vivenza, Daniela; Gallicchio, Margherita; Avanzi, Gian Carlo; Prat, Maria; Carbone, Antonino.

In: Journal of Clinical Virology, Vol. 16, No. 3, 05.2000, p. 215-224.

Research output: Contribution to journalArticle

Gaidano, G, Capello, D, Fassone, L, Gloghini, A, Cilia, AM, Ariatti, C, Buonaiuto, D, Vivenza, D, Gallicchio, M, Avanzi, GC, Prat, M & Carbone, A 2000, 'Molecular characterization of HHV-8 positive primary effusion lymphoma reveals pathogenetic and histogenetic features of the disease', Journal of Clinical Virology, vol. 16, no. 3, pp. 215-224. https://doi.org/10.1016/S1386-6532(99)00082-7
Gaidano, Gianluca ; Capello, Daniela ; Fassone, Lucia ; Gloghini, Annunziata ; Cilia, Anna Maria ; Ariatti, Cristiano ; Buonaiuto, Daniela ; Vivenza, Daniela ; Gallicchio, Margherita ; Avanzi, Gian Carlo ; Prat, Maria ; Carbone, Antonino. / Molecular characterization of HHV-8 positive primary effusion lymphoma reveals pathogenetic and histogenetic features of the disease. In: Journal of Clinical Virology. 2000 ; Vol. 16, No. 3. pp. 215-224.
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abstract = "Background: Primary effusion lymphoma (PEL) associates with HHV-8 infection, preferentially develops in immunodeficient patients and grows in the serous body cavities. PEL derives from post-germinal center, pre-terminally differentiated B-cells. The pathogenesis of PEL is unclear and the sole identified genetic lesions are human herpesvirus type-8 (HHV-8) infection in all cases and EBV infection in 70{\%} of cases. Epstein-Barr virus (EBV) infection in PEL displays a latency I phenotype. Objectives: To clarify the pathogenesis and histogenesis of PEL by investigating (1) the lymphoma karyotype; (2) the expression status of the Met tyrosine kinase receptor and of its ligand hepatocyte growth factor (HGF); (3) the molecular profile of EBV, with particular focus on mutations of EBNA-1 genes, which are thought to affect viral tumorigenicity in EBV-infected neoplasms displaying the latency I phenotype. Study design: Twenty-four PEL (nine cell lines and 15 primary specimens) formed the basis of the study. Karyotypes were investigated by conventional cytogenetics and fluorescent in situ hybridization (FISH) in selected cases. The expression status of Met and HGF was defined by multiple techniques, including RT-PCR, FACS analysis, immunocytochemistry, Western blot studies and ELISA. The molecular profile of EBNA-1 genes of EBV were investigated by DNA direct sequencing. Results: Trisomy 7, trisomy 12 and breaks at 1q21-q25 are recurrently associated with PEL. PEL consistently co-express Met and HGF both at the mRNA and protein level. Among aggressive B-cell lymphomas, Met/HGF co-expression appears to be relatively specific for PEL. The EBNA-1 gene of EBV displays a high degree of genetic heterogeneity in PEL, with no preferential association with one specific variant. Conclusions: PEL associates with recurrent chromosomal alterations, suggesting that viral infection is not sufficient for tumor development and that lesions of cellular genes may be required. The expression of Met/HGF by PEL cells may bear implications for the lymphoma proliferation and growth pattern, since Met/HGF interactions influence cell mitogenesis and motogenesis. EBV infection in PEL displays a latency I phenotype and fails to associate with specific EBNA-1 variants, suggesting that the role of EBV in PEL is not mediated by the major transforming pathways currently known in EBV positive lymphomas. Copyright (C) 2000 Elsevier Science B.V.",
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T1 - Molecular characterization of HHV-8 positive primary effusion lymphoma reveals pathogenetic and histogenetic features of the disease

AU - Gaidano, Gianluca

AU - Capello, Daniela

AU - Fassone, Lucia

AU - Gloghini, Annunziata

AU - Cilia, Anna Maria

AU - Ariatti, Cristiano

AU - Buonaiuto, Daniela

AU - Vivenza, Daniela

AU - Gallicchio, Margherita

AU - Avanzi, Gian Carlo

AU - Prat, Maria

AU - Carbone, Antonino

PY - 2000/5

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N2 - Background: Primary effusion lymphoma (PEL) associates with HHV-8 infection, preferentially develops in immunodeficient patients and grows in the serous body cavities. PEL derives from post-germinal center, pre-terminally differentiated B-cells. The pathogenesis of PEL is unclear and the sole identified genetic lesions are human herpesvirus type-8 (HHV-8) infection in all cases and EBV infection in 70% of cases. Epstein-Barr virus (EBV) infection in PEL displays a latency I phenotype. Objectives: To clarify the pathogenesis and histogenesis of PEL by investigating (1) the lymphoma karyotype; (2) the expression status of the Met tyrosine kinase receptor and of its ligand hepatocyte growth factor (HGF); (3) the molecular profile of EBV, with particular focus on mutations of EBNA-1 genes, which are thought to affect viral tumorigenicity in EBV-infected neoplasms displaying the latency I phenotype. Study design: Twenty-four PEL (nine cell lines and 15 primary specimens) formed the basis of the study. Karyotypes were investigated by conventional cytogenetics and fluorescent in situ hybridization (FISH) in selected cases. The expression status of Met and HGF was defined by multiple techniques, including RT-PCR, FACS analysis, immunocytochemistry, Western blot studies and ELISA. The molecular profile of EBNA-1 genes of EBV were investigated by DNA direct sequencing. Results: Trisomy 7, trisomy 12 and breaks at 1q21-q25 are recurrently associated with PEL. PEL consistently co-express Met and HGF both at the mRNA and protein level. Among aggressive B-cell lymphomas, Met/HGF co-expression appears to be relatively specific for PEL. The EBNA-1 gene of EBV displays a high degree of genetic heterogeneity in PEL, with no preferential association with one specific variant. Conclusions: PEL associates with recurrent chromosomal alterations, suggesting that viral infection is not sufficient for tumor development and that lesions of cellular genes may be required. The expression of Met/HGF by PEL cells may bear implications for the lymphoma proliferation and growth pattern, since Met/HGF interactions influence cell mitogenesis and motogenesis. EBV infection in PEL displays a latency I phenotype and fails to associate with specific EBNA-1 variants, suggesting that the role of EBV in PEL is not mediated by the major transforming pathways currently known in EBV positive lymphomas. Copyright (C) 2000 Elsevier Science B.V.

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KW - EBV

KW - HGF

KW - HHV-8

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