Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors.
Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors.
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DOI：
10.1002/pbc.22831
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发表时间：
2011-01
影响因子：
3.2
通讯作者：
Biegel, Jaclyn A.
中科院分区：
文献类型：
--
作者：
Eaton, Katherine W.;Tooke, Laura S.;Wainwright, Luanne M.;Judkins, Alexander R.;Biegel, Jaclyn A.
染色体带22q11.2中SMARCB 1/INI 1的生殖系突变和缺失使患者易患横纹肌样瘤和神经鞘瘤病。以前的估计表明，15-20%的横纹肌样肿瘤是由SMARCB 1的潜在生殖系异常引起的。然而，这些研究受到病例选择和无法检测基因内缺失和重复的限制。通过FISH、多重连接依赖性探针扩增（MLPA）、序列分析和基于高分辨率Illumina 610 K SNP的寡核苷酸阵列研究，分析了来自脑、肾或软组织横纹肌样肿瘤患者的100个匹配肿瘤和血液样本的SMARCB 1突变和缺失。100名患者中有35名被发现存在种系SMARCB 1异常。这些异常包括点和移码突变，基因内缺失和重复，以及包括SMARCB 1近端和远端区域的较大缺失。有9例病例证明了SMARCB 1突变拷贝的父母对子女的传播。在9例中的8例中，一个或多个家庭成员也被诊断为横纹肌样瘤或神经鞘瘤，8个家庭中的2个以符合性腺镶嵌的方式出现多个受累儿童。大约三分之一的新诊断的横纹肌样肿瘤患者由于生殖系SMARCB 1改变而具有潜在的肿瘤遗传易感性。家庭可能表现出不完全的性腺发育和性腺镶嵌，这在咨询横纹肌样瘤患者家庭时必须考虑。
Germline mutations and deletions of SMARCB1/INI1 in chromosome band 22q11.2 predispose patients to rhabdoid tumor and schwannomatosis. Previous estimates suggested that 15–20% of rhabdoid tumors were caused by an underlying germline abnormality of SMARCB1. However, these studies were limited by case selection and an inability to detect intragenic deletions and duplications. One hundred matched tumor and blood samples from patients with rhabdoid tumors of the brain, kidney, or soft tissues were analyzed for mutations and deletions of SMARCB1 by FISH, multiplex ligation-dependent probe amplification (MLPA), sequence analysis and high resolution Illumina 610K SNP based oligonucleotide array studies. Thirty-five of 100 patients were found to have a germline SMARCB1 abnormality. These abnormalities included point and frameshift mutations, intragenic deletions and duplications, and larger deletions including regions both proximal and distal to SMARCB1. There were 9 cases that demonstrated parent to child transmission of a mutated copy of SMARCB1. In 8 of the 9 cases, one or more family members were also diagnosed with rhabdoid tumor or schwannoma, and 2 of the 8 families presented with multiple affected children in a manner consistent with gonadal mosaicism. Approximately one third of newly diagnosed patients with rhabdoid tumor have an underlying genetic predisposition to tumors due to a germline SMARCB1 alteration. Families may demonstrate incomplete penetrance and gonadal mosaicism, which must be considered when counseling families of patients with rhabdoid tumor.
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影响因子：
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作者：
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