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

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. (C) 2009 UICC