Identification of a recurrent transforming UBR5-ZNF423 fusion gene in EBV-associated nasopharyngeal carcinoma.
Identification of a recurrent transforming UBR5-ZNF423 fusion gene in EBV-associated nasopharyngeal carcinoma.
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DOI：
10.1002/path.4240
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发表时间：
2013-10
影响因子：
7.3
通讯作者：
Lo, Kwok-Wai
中科院分区：
文献类型：
--
作者：
Chung, Grace T. Y.;Lung, Raymond W. M.;Hui, Angela B. Y.;Yip, Kevin Y. L.;Woo, John K. S.;Chow, Chit;Tong, Carol Y. K.;Lee, Sau-Dan;Yuen, Jessie W. F.;Lun, Samantha W. M.;Tso, Ken K. Y.;Wong, Nathalie;Tsao, Sai-Wah;Yip, Timothy T. C.;Busson, Pierre;Kim, Hyungtae;Seo, Jeong-Sun;O'Sullivan, Brian;Liu, Fei-Fei;To, Ka-Fai;Lo, Kwok-Wai
关键词：
鼻咽癌（NPC）是一种独特的头颈癌，常见于中国南部、东南亚和北非。鼻咽癌的发展和逐步进展涉及 Epstein-Barr 病毒 (EBV) 感染的鼻咽上皮细胞群克隆扩增过程中多种总体遗传变化的积累。在这里，使用双端全转录组测序，我们在一组 EBV 阳性肿瘤系中发现了许多嵌合融合转录本。在这些转录物中，从 NPC 细胞系 C666-1 中鉴定出 8q22.3 上的泛素蛋白连接酶 E3 成分 n-recognin 5 (UBR5) 和 16q12.1 上的锌指蛋白 423 (ZNF423) 的新型融合，在 12/144 (8.3%) 的原发性肿瘤中反复检测到。该融合基因包含UBR5的外显子1和ZNF423的外显子7-9，并产生94个氨基酸的嵌合蛋白，包括ZNF423的原始C端EBF结合域(ZF29-30)。值得注意的是，具有 UBR5-ZNF423 重排的 NPC 细胞的生长依赖于该融合蛋白的表达。通过融合特异性 siRNA 敲低 UBR5-ZNF423 显着抑制 C666-1 细胞的细胞增殖和集落形成能力。 UBR5-ZNF423融合体的转化能力也在NIH3T3成纤维细胞中得到证实。 NIH3T3 成纤维细胞中 UBR5-ZNF423 的组成型表达显着增强了其在软琼脂中的贴壁独立生长，并诱导裸鼠模型中的肿瘤形成。这些发现表明，UBR5-ZNF423 蛋白的表达可能通过改变 EBF（早期 B 细胞因子）的活性来促进一部分 NPC 的转化。致癌性 UBR5-ZNF423 的鉴定为鼻咽癌的治疗干预提供了新的潜在机会。 © 2013 作者。 《病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。
Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer which is prevalent in southern China, south-east Asia and northern Africa. The development and stepwise progression of NPC involves accumulation of multiple gross genetic changes during the clonal expansion of Epstein–Barr virus (EBV)-infected nasopharyngeal epithelial cell population. Here, using paired-end whole-transcriptome sequencing, we discovered a number of chimeric fusion transcripts in a panel of EBV-positive tumour lines. Among these transcripts, a novel fusion of ubiquitin protein ligase E3 component n-recognin 5 (UBR5) on 8q22.3 and zinc finger protein 423 (ZNF423) on 16q12.1, identified from the NPC cell line C666-1, was recurrently detected in 12/144 (8.3%) of primary tumours. The fusion gene contains exon 1 of UBR5 and exons 7–9 of ZNF423 and produces a 94 amino acid chimeric protein including the original C-terminal EBF binding domain (ZF29-30) of ZNF423. Notably, the growth of NPC cells with UBR5–ZNF423 rearrangement is dependent on expression of this fusion protein. Knock-down of UBR5–ZNF423 by fusion-specific siRNA significantly inhibited the cell proliferation and colony-forming ability of C666-1 cells. The transforming ability of UBR5–ZNF423 fusion was also confirmed in NIH3T3 fibroblasts. Constitutive expression of UBR5–ZNF423 in NIH3T3 fibroblasts significantly enhanced its anchorage-independent growth in soft agar and induced tumour formation in a nude mouse model. These findings suggest that expression of UBR5–ZNF423 protein might contribute to the transformation of a subset of NPCs, possibly by altering the activity of EBFs (early B cell factors). Identification of the oncogenic UBR5–ZNF423 provides new potential opportunities for therapeutic intervention in NPC. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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影响因子：
64.5
作者：
Chaki M;Airik R;Ghosh AK;Giles RH;Chen R;Slaats GG;Wang H;Hurd TW;Zhou W;Cluckey A;Gee HY;Ramaswami G;Hong CJ;Hamilton BA;Cervenka I;Ganji RS;Bryja V;Arts HH;van Reeuwijk J;Oud MM;Letteboer SJ;Roepman R;Husson H;Ibraghimov-Beskrovnaya O;Yasunaga T;Walz G;Eley L;Sayer JA;Schermer B;Liebau MC;Benzing T;Le Corre S;Drummond I;Janssen S;Allen SJ;Natarajan S;O'Toole JF;Attanasio M;Saunier S;Antignac C;Koenekoop RK;Ren H;Lopez I;Nayir A;Stoetzel C;Dollfus H;Massoudi R;Gleeson JG;Andreoli SP;Doherty DG;Lindstrad A;Golzio C;Katsanis N;Pape L;Abboud EB;Al-Rajhi AA;Lewis RA;Omran H;Lee EY;Wang S;Sekiguchi JM;Saunders R;Johnson CA;Garner E;Vanselow K;Andersen JS;Shlomai J;Nurnberg G;Nurnberg P;Levy S;Smogorzewska A;Otto EA;Hildebrandt F
通讯作者：
Hildebrandt F
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
影响因子：
--
作者：
BERNHEIM, A;ROUSSELET, G;TURSZ, T
通讯作者：
TURSZ, T
影响因子：
8
作者：
Warming, S;Suzuki, T;Copeland, NG
通讯作者：
Copeland, NG
影响因子：
11.2
作者：
Zhao, Lisa Y.;Niu, Yuxin;Liao, Daiqing
通讯作者：
Liao, Daiqing