Mutation analysis of tumor necrosis factor alpha-induced protein 3 gene in Hodgkin lymphoma
Mutation analysis of tumor necrosis factor alpha-induced protein 3 gene in Hodgkin lymphoma
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DOI：
10.1016/j.prp.2016.11.001
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发表时间：
2017-01-01
影响因子：
2.8
通讯作者：
Petersen, Iver
中科院分区：
文献类型：
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作者：
Etzel, Barbara-Magdalena;Gerth, Melanie;Petersen, Iver
目的：霍奇金细胞和里德-斯滕伯格 (HRS) 细胞（经典霍奇金淋巴瘤 (CHL) 的恶性细胞）的存活和增殖依赖于核因子 kappa B (NF-kappa B) 的组成型激活。 A20 由 TNF α 诱导蛋白 3 (TNFAIP(3)) 编码，是 NF-κ B 的抑制剂之一，被发现因 CHL 中的缺失和/或点突变而失活。 方法：通过 PCR 和直接测序对 37 例 CHL 患者进行 TNFAIP3 突变检测。此外，通过免疫组织化学评估A20的蛋白表达。通过 EBV EBER 显色原位杂交 (ISH) 确定 HL 样本的 Epstein-Barr 病毒 (EBV) 状态。结果：我们在 37 例调查病例中发现了 8 例突变阳性病例 (22%)。突变在结节性硬化症亚型中最常见。我们的结果揭示了携带 A20 突变的病例 A20 染色呈阴性的趋势。 A20突变阳性CHL病例均未表现出EBV感染。结论：我们的研究证实了TNFAIP3抑癌基因与CHL有关。 A20 可能代表人类淋巴瘤的抑制因子，并提供慢性炎症和癌症之间的关键分子联系。 A20 突变阳性 CHL 病例均未表现出 EBV 感染。这一事实表明 TNFAIP(3) 失活和 EBV 感染在 CHL 发病机制中具有互补作用，并可能代表进一步研究的一个有趣点。 (C) 2016 爱思唯尔有限公司。版权所有。
Aims: Survival and proliferation of Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (CHL), are dependent on constitutive activation of nuclear factor kappa B (NF-kappa B). A20, encoded by TNF alpha-induced protein 3 (TNFAIP(3)), one of the inhibitors of NF-kappa B, was found to be inactivated by deletions and/or point mutations in CHL.Methods: TNFAIP3 mutations were examined in 37 patients with CHL by using PCR and direct sequencing. In addition, protein expression of A20 was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) status of HL samples was determined by EBV EBER chromogenic in situ hybridization (ISH).Results: We identified 8 mutation positive cases in a collective of 37 investigated cases (22%). Mutations were most frequent in the nodular sclerosis subtype. Our results revealed the tendency that cases harboring A20 mutations were negative for A20 staining. None of A20 mutation-positive CHL cases showed EBV infection.Conclusions: Our study confirms the involvement of the TNFAIP3 tumor suppressor gene in CHL. A20 may represent a suppressor of human lymphoma and provide a critical molecular link between chronic inflammation and cancer. None of A20 mutation-positive CHL cases showed EBV infection. This fact suggests complementing functions of TNFAIP(3) inactivation and EBV infection in CHL pathogenesis and may represent an interesting point of further investigations. (C) 2016 Elsevier GmbH. All rights reserved.