Mutations of NFKBIA, encoding I kappa B alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases

Lake, A. et al. (2009) Mutations of NFKBIA, encoding I kappa B alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. International Journal of Cancer, 125(6), pp. 1334-1342. (doi: 10.1002/ijc.24502)

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Abstract

A consistent feature of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF-kappa B transcription factors. In Epstein-Barr virus (EBV)-associated cases of cHL, expression of viral antigens most probably leads to NF-kappa B activation but for non-EBV-associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding I kappa B alpha, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non-EBV-associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non-EBV-associated cases but the majority of these cases had wild-type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF-kappa B, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jarrett, Professor Ruth and Crae, Mrs Shauna and Cordano, Dr Pablo and Lake, Ms Annette and Shield, Dr Lesley
Authors: Lake, A., Shield, L.A., Cordano, P., Chui, D.T.Y., Osborne, J., Crae, S., Wilson, K.S., Tosi, S., Knight, S.J.L., Gesk, S., Siebert, R., Hay, R.T., and Jarrett, R.F.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:International Journal of Cancer
ISSN:0020-7136

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