DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.
DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.
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DOI：
10.1001/jama.2010.1910
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发表时间：
2011-01-05
影响因子：
120.7
通讯作者：
Tischkowitz, Marc
中科院分区：
文献类型：
--
作者：
Frio, Thomas Rio;Bahubeshi, Amin;Kanellopoulou, Chryssa;Hamel, Nancy;Niedziela, Marek;Sabbaghian, Nelly;Pouchet, Carly;Gilbert, Lucy;O'Brien, Paul K.;Serfas, Kim;Broderick, Peter;Houlston, Richard S.;Lesueur, Fabienne;Bonora, Elena;Muljo, Stefan;Schimke, R. Neil;Bouron-Dal Soglio, Dorothee;Arseneau, Jocelyne;Schultz, Kris Ann;Priest, John R.;Nguyen, Van-Hung;Ruben Harach, H.;Livingston, David M.;Foulkes, William D.;Tischkowitz, Marc
非毒性多结节性甲状腺肿（MNG）是常见于一般人群，但很少有人知道这种疾病的潜在遗传易感性。MNG的家族性病例已被报道，并且有五个这样的家族也包含卵巢支持-间质细胞瘤（SLCT）的个体。DICER 1（一种编码RNase III核糖核酸内切酶的基因）的种系突变最近在受胸膜肺母细胞瘤（PPB）影响的家族中被发现，其中一些包括MNG和性腺肿瘤（如SLCT）的病例。确定在PPB缺失的情况下，家族性MNG伴或不伴SLCT是否由DICER 1突变引起。从2009年9月到2010年9月，我们研究了两个MNG家族和三个MNG/SLCT家族。我们筛选了受影响的先证者的DICER 1基因突变。我们研究了来自家族成员的血液淋巴细胞、MNG和SLCT组织的野生型等位基因缺失（杂合性缺失）、DICER 1表达和microRNA失调。在有和没有SLCT的家族性MNG中检测生殖系DICER 1基因突变。我们在所有五个家族中鉴定并表征了生殖系DICER 1突变。三个SLCT的分子分析显示DICER 1没有杂合性丢失，两个可用样本的IHC分析显示DICER 1在支持细胞中强表达，但在间质细胞中弱染色。对来自家族性MNG病例中受影响和未受影响成员的淋巴母细胞样细胞系的RNA进行microRNA分析，发现DICER 1突变携带者中存在miRNA干扰。DICER 1突变易患家族性MNG和SLCT MNG，独立于PPB和生殖系DICER 1突变导致miRNA的失调。这可能是进一步研究肿瘤发生的一种可能的新机制。
Non-toxic multinodular goiter (MNG) is frequently observed in the general population, but little is known about the underlying genetic susceptibility to this disease. Familial cases of MNG have been reported and there are five such published families which also contain individuals with Sertoli-Leydig cell tumors of the ovary (SLCT). Germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have recently been identified in families affected pleuropulmonary blastoma (PPB), some of whom include cases of MNG and gonadal tumors such as SLCT. To determine whether familial MNG with or without SLCT in the absence of PPB was caused by mutations in DICER1. From September 2009 to September 2010, we studied two MNG families and three MNG/SLCT families. We screened affected probands for mutations in the DICER1 gene. We investigated blood lymphocytes, MNG and SLCT tissue from family members for loss of the wild-type allele (loss of heterozygosity), DICER1 expression and microRNA dysregulation. Detection of germline DICER1 gene mutations in familial MNG with and without SLCT. We identified and characterized germline DICER1 mutations in all five families. Molecular analysis of the three SLCTs showed no loss of heterozygosity at DICER1, and IHC analysis in two available samples showed strong expression of DICER1 in Sertoli cells, but weak staining of Leydig cells. MicroRNA profiling of RNA derived from lymphoblastoid cell lines from both affected and unaffected members of the familial MNG cases revealed miRNA perturbations in DICER1 mutation carriers. DICER1 mutations predispose to both familial MNG and MNG with SLCT, independent of PPB and germline DICER1 mutations lead to dysregulation of miRNA. This could be investigated further as a possible novel mechanism of tumorigenesis.
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影响因子：
15.9
作者：
Frio, Thomas Rio;Wade, Nicholas M.;Rivolta, Carlo
通讯作者：
Rivolta, Carlo
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
3.2
作者：
Niedziela, Marek
通讯作者：
Niedziela, Marek
DOI：
10.1126/science.1174334
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hill DA;Ivanovich J;Priest JR;Gurnett CA;Dehner LP;Desruisseau D;Jarzembowski JA;Wikenheiser-Brokamp KA;Suarez BK;Whelan AJ;Williams G;Bracamontes D;Messinger Y;Goodfellow PJ
通讯作者：
Goodfellow PJ
DOI：
10.1073/pnas.0710228105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Chen, Jian-Fu;Murchison, Elizabeth P.;Wang, Da-Zhi
通讯作者：
Wang, Da-Zhi