Research from University of Duisburg-Essen provide new insights into lymphoma
2009 JUL 14 - (NewsRx.com) -- According to a study from Essen, Germany, "Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappa B (NF-kappa B). NF-kappa B activation through various stimuli is negatively regulated by the zinc finger protein A20." "To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV+) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV- cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappa B target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappa B activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappa B activity, as a novel tumor suppressor gene in cHL and PMBL," wrote R. Schmitz and colleagues, University of Duisburg-Essen. The researchers concluded: "The significantly higher frequency of TNFAIP3 mutations in EBV- than EBV+ cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis." Schmitz and colleagues published the results of their research in the Journal of Experimental Medicine (TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. Journal of Experimental Medicine, 2009;206(5):981-989). For additional information, contact R. Kuppers, University of Duisburg Essen, School Medical, Institute Cell Biology Cancer Research, D-45122 Essen, Germany. The publisher of the Journal of Experimental Medicine can be contacted at: Rockefeller University Press, 1114 First Avenue, 4TH FL, New York, NY 10021, USA. Keywords: Germany, Essen, B-Cell Lymphoma, Chronic Fatigue Syndrome, EBV, Epstein-Barr Virus, Experimental Medicine, Genetics, Hematology, Herpes, Herpesvirus, Oncology, Tumor Suppression, Virology, University of Duisburg-Essen. This article was prepared by Virus Weekly editors from staff and other reports. Copyright 2009, Virus Weekly via NewsRx.com.
|
