Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.
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Jungnickel B, Staratschek-Jox A, Brauninger A, Spieker T, Wolf J, Diehl V, Hansmann ML, Rajewsky K, Kuppers R
Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.
J Exp Med. 2000 Jan 17;191(2):395-402.
- PubMed ID
- 10637284 [ View in PubMed]
- Abstract
Members of the nuclear factor (NF)-kappaB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-kappaB (IkappaB) family, whose degradation activates NF-kappaB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-kappaB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-kappaB activation). There was no evidence for IkappaBalpha mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IkappaBalpha mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IkappaBalpha defects in the pathogenesis of HL and implying that IkappaBalpha is a tumor suppressor gene.