A20, encoded by TNF alpha-induced protein 3 (TNFAIP<sub>3)</sub>, one of the inhibitors of NF-kB, was found to be inactivated by deletions and/or point mutations in CHL.
The low mutation frequency and the absence of biallelic destructive mutations propose a minor contribution of NFKBIA and TNFAIP3 mutations to the NF-kappaB activity of NLPHL, suggesting different mechanisms of NF-kappaB activation in NLPHL and cHL.
The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.