RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer.
RNF43 mutations are recurrent in Chinese patients with mucinous ovarian carcinoma but absent in other subtypes of ovarian cancer.
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DOI：
10.1016/j.gene.2013.08.054
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发表时间：
2013-11
期刊：
影响因子：
3.5
通讯作者：
Y. Zou;Feng Wang;Faying Liu;Mei-zhen Huang;Wei Li;Xiao-Qun Yuan;Ouping Huang;M. He
中科院分区：
文献类型：
--
作者：
Y. Zou;Feng Wang;Faying Liu;Mei-zhen Huang;Wei Li;Xiao-Qun Yuan;Ouping Huang;M. He
环指蛋白43（Ring finger protein 43，RNF 43）是一种E3泛素-蛋白连接酶，它从E2泛素缀合酶接受泛素并直接将泛素转移到靶底物蛋白。最近，大规模测序工作已经确定了胰腺和卵巢粘液癌中普遍存在的RNF 43突变。在本研究中，我们对251例不同亚型的卵巢癌患者的RNF 43基因编码序列进行了测序，以确定RNF 43基因突变的存在。15例卵巢粘液癌患者中有2例（13.3%）发现了RNF 43基因的2个新的杂合性非同义突变，这些突变在进化上高度保守，而在其他样本中未检测到突变。此外，RNF 43突变的样本均未携带DICER 1（dicer 1，核糖核酸酶III型）、PPP 2 R1 A（蛋白磷酸酶2，调节亚基A，α）、TRRAP（转化/转录结构域相关蛋白）和DNMT 3A（DNA（胞嘧啶-5-）-甲基转移酶3 α）热点突变。复发性RNF 43突变存在于粘液性卵巢癌中，暗示这些突变可能在这些患者的肿瘤发生中起关键作用，而DICER 1，PPP 2 R1 A，TRRAP和DNMT 3A热点突变的缺失表明这些遗传改变可能与RNF 43突变在这些个体中不起协同作用。此外，RNF 43突变在其他亚型卵巢癌中的缺失暗示RNF 43突变可能不积极参与这些疾病的发病机制。
Ring finger protein 43 (RNF43) is an E3 ubiquitin-protein ligase that accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and directly transfers the ubiquitin to targeted substrate proteins. Recently, large-scale sequencing efforts have identified prevalent RNF43 mutations in pancreatic and ovarian mucinous carcinomas. In the present study, we sequenced the entire coding sequences of RNF43 in 251 Chinese patients with distinct subtypes of ovarian cancers for the presence of RNF43 mutations. A total of 2 novel heterozygous nonsynonymous RNF43 mutations were identified in 2 out of 15 (13.3%) patients with mucinous ovarian carcinoma, these mutations were evolutionarily highly conserved; while no mutation was detected in other samples. In addition, none of the RNF43-mutated samples harbored DICER1 (dicer 1, ribonuclease type III), PPP2R1A (protein phosphatase 2, regulatory subunit A, alpha), TRRAP (transformation/transcription domain-associated protein) and DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha) hot-spot mutations. Recurrent RNF43 mutations existed in mucinous ovarian carcinomas implicated that these mutations might play crucial roles in the tumorigenesis of these patients, while the absence of DICER1, PPP2R1A, TRRAP and DNMT3A hot-spot mutations suggested that these genetic alterations might not play synergistic roles with RNF43 mutations in these individuals. Additionally, the absence of RNF43 mutations in other subtypes of ovarian carcinoma implicated that RNF43 mutations might not be actively involved in the pathogenesis of these disorders.