Different genetic alteration of A20 in a Sézary syndrome case with Vα2-Jα22 T cell clone.

BackgroundThe comprehensive genetic alterations underlying the pathogenesis of Sezary syndrome (SS) remains largely unknown. Previous studies showed that alterations of tumor necrosis factor--induced protein 3 gene (TNFAIP3; A20) are frequent in SS. In this study, we characterized the mutation and polymorphisms of A20 in a case with SS and compared with the genetic feature of A20 in T-cell acute lymphoblastic leukemia (T-ALL). MethodsUsing a novel approach based on the combination of fine-tiling array comparative genomic hybridization ( and ligation-mediated polymerase chain reaction (LM-PCR) to identify SS clone, the polymorphisms in the A20 gene (promoter, exons 2-9 [coding region] and 3UTR) were detected by PCR and sequencing. ResultsThe malignant SS clone was identified as TCR V2-J22 rearrangement without deletion at the A20 loci (6q23-27 region) in the SS case. Six polymorphisms were identified, all of them are belonging to single nucleotide polymorphisms (SNPs) that are recorded in genebank: rs5029924, rs5029937, rs2230926, rs582757 and rs77191406, while rs2307859 was not identified in the SS sample, which is found in all T-ALL. The alteration pattern of A20 in this case seemed different from the T-ALL samples, in contrast, it is similar to the alteration of A20 in samples from rheumatoid arthritis or systemic lupus erythematosus with poor clinical outcome and cancer developing. ConclusionsThe genetic alteration of A20 in the SS case was different from the T-ALL samples and similar to the cases with refractory autoimmune disease and related to tumorigenesis. The findings lead to discuss whether such SNPs of A20 may link the refractory autoimmune inflammation and the tumorigenesis.