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

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Item Type:	Article
Title:	Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells
Creators Name:	Emmerich, F., Theurich, S., Hummel, M., Haeffker, A., Vry, M.S., Doehner, K., Bommert, K., Stein, H. and Doerken, B.
Abstract:	The pathogenesis of Hodgkin lymphoma (HL) is still unclear. Previous investigations have demonstrated constitutive nuclear activity of the transcription factor NF kappa B (NF-{kappa}B) in Hodgkin/Reed-Sternberg (HRS) cells as an important prerequisite in protecting these cells from apoptosis. As a molecular mechanism leading to constitutive NF-{kappa}B activity in HRS cells, mutations of the NF-{kappa}B inhibitor I kappa B alpha (I{kappa}B{alpha}) have recently been identified in classical (c) HL-derived cell lines in a patient with cHL. In the present study, the NF-{kappa}B inhibitor I kappa B epsilon (I{kappa}BE) has been analysed for somatic mutations in the same group of six patients already studied for I{kappa}B{alpha} 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 I{kappa}BE gene was found. These results, in combination with recently described I{kappa}B{alpha} mutations, indicate that defective NF-{kappa}B inhibitors appear more frequent than previously thought and might explain the constitutive nuclear activity of NF-{kappa}B in a significant proportion of cHL cases.
Keywords:	Hodgkin, I Kappa B Epsilon Mutations, NF Kappa B
Source:	Journal of Pathology
ISSN:	0022-3417
Publisher:	John Wiley & Sons Ltd
Volume:	201
Number:	3
Page Range:	413-420
Date:	November 2003
Official Publication:	https://doi.org/10.1002/path.1454
PubMed:	View item in PubMed

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