To determine the role of the t(2;5) translocation in these diseases, we developed a DNA-based polymerase chain reaction (PCR)/Southern blot assay to detect this translocation at the genomic level in lymphomatoid papulosis (14 cases), primary cutaneous CD30+ large cell lymphoma of T-lineage (10 cases) and Hodgkin's disease (13 cases).
To elucidate the molecular mechanism of CD30-mediated apoptosis of ALCL, we compared the gene expression profiles of t(2;5)(p23;q35)-positive ALCL with those of HL altered by CD30 agonistic stimulation.
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.
Overall, our results suggest that germline mutations of NFKBIA are not a significant cause of familial aggregation of HL but may contribute to inherited susceptibility to HL.
We suggest that the observed IkappaBalpha mutations contribute to constitutive NF-kappaB activity in cultured and primary HRS cells and are therefore involved in the pathogenesis of these Hodgkin's disease (HD) patients.
These results suggest that the wild allele of the GSTP1 gene is linked to an increased risk and high aggressiveness of the HL in our cases but they should be confirmed by further studies with larger cohorts of patients and controls.
The GSTP1rs1695 A-allele reduced the risk for HL (GG vs. AG, OR 0.64 [0.42-0.99], p = 0.04; GG vs. AG/AA combined genotypes, OR 0.70 [0.47-1.04], p = 0.07), and the GSTT1 deleted genotype increased the risk for HL (OR 3.17 [1.97-5.09], p < 0.001) regardless of age.