A20 (TNFAIP3) deletion in Epstein-Barr virus-associated lymphoproliferative disorders/lymphomas.
A20 (TNFAIP3) deletion in Epstein-Barr virus-associated lymphoproliferative disorders/lymphomas.
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DOI：
10.1371/journal.pone.0056741
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yoshino T
中科院分区：
文献类型：
--
作者：
Ando M;Sato Y;Takata K;Nomoto J;Nakamura S;Ohshima K;Takeuchi T;Orita Y;Kobayashi Y;Yoshino T
核因子(NF)-κB通路的负调节因子A20 （TNFAIP3）在几种类型的淋巴瘤中失活；尤其是弥漫性大b细胞淋巴瘤（DLBCL）、经典霍奇金淋巴瘤和粘膜相关淋巴组织结外边缘区淋巴瘤。这些发现提示NF-κB活化与A20失活有关。最近，在eb病毒（EBV）相关淋巴瘤中也观察到A20失活；然而，这一现象并没有得到很好的调查。此外，NF-κB是活化b细胞样（ABC）型DLBCL的关键分子；ebv相关DLBCL为ABC类型。因此，我们将重点放在ebv相关淋巴增生性疾病/淋巴瘤中的A20缺失上。采用荧光原位杂交分析，13例脓胸相关淋巴瘤（PAL）患者中有4例（31%），20例鼻型NK/T细胞淋巴瘤（NKTLs）患者中有3例（15%），8例ebv阳性老年DLBCL患者中有1例（DLBCL-e）（13%）， 11例甲氨蝶呤相关淋巴细胞增生性疾病（MTX-LPD）患者中均未发现A20缺失（0%）。在A20缺失的样本中，4个A20缺失的PAL样本和A20缺失的DLBCL-e样本中均检测到EBV潜伏膜蛋白1 （LMP-1）的表达，而3个NKTL样本中均未检测到。这一发现表明，A20缺失与EBV淋巴瘤的潜伏期模式没有直接关系，尽管这种缺失可能与诊断类别有关。免疫组织学上，13例PAL样本中2例（15%）、11例MTX-LPD样本中1例（9%）、20例NKTL（0%）和8例DLBCL-e样本中均无A20蛋白。综上所述，A20缺失和/或表达功能障碍常与PAL相关，A20异常可能与PAL的发病机制有关。
A negative regulator of the nuclear factor (NF)-κB pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-κB activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-κB is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL.
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DOI：
10.1158/1078-0432.ccr-11-3169
发表时间：
2012-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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通讯作者：
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影响因子：
20.3
作者：
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影响因子：
56.9
作者：
Lenz, Georg;Davis, R. Eric;Staudt, Louis M.
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TNFAIP3（A20）是霍奇金淋巴瘤和原发性纵隔B细胞淋巴瘤中的肿瘤抑制基因。
DOI：
10.1084/jem.20090528
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Schmitz R;Hansmann ML;Bohle V;Martin-Subero JI;Hartmann S;Mechtersheimer G;Klapper W;Vater I;Giefing M;Gesk S;Stanelle J;Siebert R;Küppers R
通讯作者：
Küppers R
影响因子：
64.8
作者：
Compagno, Mara;Lim, Wei Keat;Grunn, Adina;Nandula, Subhadra V.;Brahmachary, Manisha;Shen, Qiong;Bertoni, Francesco;Ponzoni, Maurilio;Scandurra, Marta;Califano, Andrea;Bhagat, Govind;Chadburn, Amy;Dalla-Favera, Riccardo;Pasqualucci, Laura
通讯作者：
Pasqualucci, Laura