Zhou Lingling, Zheng Haitao, Huang Xin, Zhu Lihua, Wu Suijing, Zeng Chengwu, Yang Lijian, Chen Shaohua, Luo Gengxin, Du Xin, Li Yangqiu
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Asia Pac J Clin Oncol. 2018 Apr;14(2):e116-e123. doi: 10.1111/ajco.12672. Epub 2017 Mar 14.
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).
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.
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.
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.
蕈样肉芽肿综合征（SS）发病机制背后的综合基因改变在很大程度上仍不清楚。先前的研究表明，肿瘤坏死因子-α诱导蛋白3基因（TNFAIP3；A20）的改变在SS中很常见。在本研究中，我们对1例SS患者A20的突变和多态性进行了特征分析，并与T细胞急性淋巴细胞白血病（T-ALL）中A20的基因特征进行了比较。
使用基于精细平铺阵列比较基因组杂交和连接介导的聚合酶链反应（LM-PCR）相结合的新方法来鉴定SS克隆，通过PCR和测序检测A20基因（启动子、外显子2-9[编码区]和3'UTR）中的多态性。
在该SS病例中，恶性SS克隆被鉴定为TCR Vα2-Jα22重排，A20基因座（6q23-27区域）无缺失。鉴定出6种多态性，所有这些多态性均属于基因库中记录的单核苷酸多态性（SNP）：rs5029924、rs5029937、rs2230926、rs582757和rs77191406，而rs2307859在SS样本中未被鉴定，该SNP在所有T-ALL中均有发现。该病例中A20的改变模式似乎与T-ALL样本不同，相反，它类似于类风湿性关节炎或系统性红斑狼疮样本中A20的改变，这些样本临床预后较差且会发生癌症。
SS病例中A20的基因改变与T-ALL样本不同，与难治性自身免疫性疾病病例相似，且与肿瘤发生有关。这些发现引发了关于A20的此类SNP是否可能将难治性自身免疫性炎症与肿瘤发生联系起来的讨论。
