ROQUIN/RC3H1 alterations are not found in angioimmunoblastic T-cell lymphoma.

ROQUIN/RC3H1 alterations are not found in angioimmunoblastic T-cell lymphoma.
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DOI:
10.1371/journal.pone.0064536
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Delfau-Larue MH
Delfau-Larue MH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Auguste T;Travert M;Tarte K;Amé-Thomas P;Artchounin C;Martin-Garcia N;de Reynies A;de Leval L;Gaulard P;Delfau-Larue MH

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血管免疫母细胞性T细胞淋巴瘤(AITL)是最常见的T细胞淋巴瘤实体之一。滤泡辅助性T淋巴细胞(TFH)被认为是肿瘤成分的正常细胞对应物。尽管克隆T细胞的功能和很少描述复发性细胞遗传学异常,驱动致癌事件尚未确定到目前为止。最近有报道称,在小鼠中,Roquin/Rc 3 h1(一种RING型E3泛素连接酶)的杂合失活重现了许多与人类AITL相关的临床、组织学和细胞特征。在这项研究中,我们探讨了ROQUIN改变是否可能是人类AITL致癌过程中的初始事件。使用微阵列和RT-PCR分析,我们研究了从AITL(n = 8)和反应性扁桃体(n = 12)纯化的TFH肿瘤细胞中ROQUIN转录物的水平,发现两者中ROQUIN表达水平相似。    此外,我们还证明了ROQUIN蛋白由AITL TFH(PD 1+)细胞表达。然后,我们分析了12个富含肿瘤细胞的AITL样品中的ROQUIN编码序列,并在任何样品中均未发现突变。最后,我们分析了MiR 101的表达,MiR 101是ROQUIN参与ICOS表达调节的假定伴侣,并发现肿瘤和反应性TFH中的表达水平相似。总之,这项研究表明,ROQUIN基因的改变和miR 101表达的失调都不可能是AITL中的频繁复发事件。
Angioimmunoblastic T-cell Lymphoma (AITL) is one of the most frequent T-cell lymphoma entities. Follicular helper T lymphocytes (TFH) are recognized as the normal cellular counterpart of the neoplastic component. Despite a clonal T-cell feature and few described recurrent cytogenetic abnormalities, a driving oncogenic event has not been identified so far. It has been recently reported that in mice, heterozygous inactivation of Roquin/Rc3h1, a RING type E3 ubiquitine ligase, recapitulates many of the clinical, histological, and cellular features associated with human AITL. In this study we explored whether ROQUIN alterations could be an initial event in the human AITL oncogenic process. Using microarray and RT-PCR analyses, we investigated the levels of ROQUIN transcripts in TFH tumor cells purified from AITL (n = 8) and reactive tonsils (n = 12) and found similar levels of ROQUIN expression in both. Moreover, we also demonstrated that ROQUIN protein was expressed by AITL TFH (PD1+) cells. We then analysed ROQUIN coding sequence in 12 tumor cell-rich AITL samples and found no mutation in any of the samples. Finally, we analysed the expression of MiR101, a putative partner of ROQUIN involved in the modulation of ICOS expression and found similar levels of expression in tumor and reactive TFH. Altogether, this study shows that neither alteration of ROQUIN gene nor deregulation of miR101 expression is likely to be a frequent recurrent event in AITL.
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