Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells

J Pathol. 2003 Nov;201(3):413-20. doi: 10.1002/path.1454.


The pathogenesis of Hodgkin lymphoma (HL) is still unclear. Previous investigations have demonstrated constitutive nuclear activity of the transcription factor NF kappa B (NF-kappaB) in Hodgkin/Reed-Sternberg (HRS) cells as an important prerequisite in protecting these cells from apoptosis. As a molecular mechanism leading to constitutive NF-kappaB activity in HRS cells, mutations of the NF-kappaB inhibitor I kappa B alpha (IkappaBalpha) have recently been identified in classical (c) HL-derived cell lines in a patient with cHL. In the present study, the NF-kappaB inhibitor I kappa B epsilon (IkappaBepsilon) has been analysed for somatic mutations in the same group of six patients already studied for IkappaBalpha mutations, as well as in cHL-derived cell lines. In one cHL-derived cell line (L428), a hemizygous frame-shift mutation generating a pre-terminal stop codon resulting in a severely truncated protein was found. Moreover, in the HRS cells of one patient, a hemizygous mutation affecting the 5'-splicing site of intron 1 of the IkappaBepsilon gene was found. These results, in combination with recently described IkappaBalpha mutations, indicate that defective NF-kappaB inhibitors appear more frequent than previously thought and might explain the constitutive nuclear activity of NF-kappaB in a significant proportion of cHL cases.

MeSH terms

  • Blotting, Western / methods
  • Chromosome Mapping / methods
  • Cloning, Molecular / methods
  • Exons / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / pathology
  • Humans
  • I-kappa B Proteins / genetics*
  • Mutation / genetics
  • NF-kappa B / antagonists & inhibitors*
  • Neoplasm Proteins / analysis
  • Polymerase Chain Reaction / methods
  • RNA, Neoplasm / analysis
  • Reed-Sternberg Cells
  • Tumor Cells, Cultured


  • I-kappa B Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • RNA, Neoplasm