title: Different genetic alteration of A20 in a Sézary syndrome case with Vα2-Jα22 T cell clone.
abstract: BACKGROUND
  The comprehensive genetic alterations underlying the pathogenesis of Sézary syndrome (SS) remains largely unknown. Previous studies showed that alterations of tumor necrosis factor-α-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).
  
  
  METHODS
  Using 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 3'UTR) were detected by PCR and sequencing.
  
  
  RESULTS
  The malignant SS clone was identified as TCR Vα2-Jα22 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.|Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Hematology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Rheumatism and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou, China.
authors.forename: Suijing
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.|Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Chengwu
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Gengxin
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Hematology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.affiliation: Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.|Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.|Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D006801:Humans; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D012751:Sezary Syndrome / Q000235:genetics* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics*
chemical_list: C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20 gene; Sézary syndrome; T cell clone; TCR rearrangement; polymorphisms