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首页> 外文会议>Academic Committee Conference of Shanghai key lab of stomatology >A novel mutation of the PTCH1 gene activates the Shh/Gli signaling pathway in a Chinese family with nevoid basal cell carcinoma syndrome
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A novel mutation of the PTCH1 gene activates the Shh/Gli signaling pathway in a Chinese family with nevoid basal cell carcinoma syndrome

机译：PTCH1基因的新型突变激活了中国患有避免基底细胞癌综合征的中国家庭的Shh / Gli信号通路

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Objective: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a predisposition to neoplasms and developmental abnormalities. Mutation of the PTCH1 gene, which is considered to be responsible for NBCCS, was investigated in a Chinese NBCCS family in this study. Methods: Cenomic DNA was isolated from blood samples of all eight living individuals in this family. Mutation analysis of PTCH1 was done by amplified polymerase chain reaction and direct sequencing. Biophysical predictions of the altered protein were made using various bioinformatics tools. To determine the action of the mutated protein, the expression of Gli1 and Cli2 was investigated by immunohistochemistry. Results: A novel FTCH1 mutation at 897C → A in exon4 was identified in all four affected members. This mutation was not found in any unaffected members of this family or in 100 unrelated healthy Chinese people. The mutation causes amino acid replacement 237E → K in the first large extracellular loop of the PTCH1 protein which is required for Sonic Hedgehog (Shh) binding. This mutation changes the protein's biochemical properties and protein activity, resulting in subsequent activation of transcription factors, Cli1 and Cli2, in the Shh/Cli signaling pathway. Immunohistochemistry showed overexpression of Clil and Cli2 in the keratocystic odontogenic tumor (KCOT) tissues.
机译：目的：Nevoid基底细胞癌综合征（NBCCS）是一种常染色体显性遗传疾病，其特征是易患肿瘤和发育异常。在这项研究中，研究了中国NBCCS家族中PTCH1基因的突变，该基因被认为是造成NBCCS的原因。方法：从该家庭所有八个活着的人的血液样本中分离出基因组DNA。通过扩增的聚合酶链反应和直接测序对PTCH1进行突变分析。使用各种生物信息学工具对改变的蛋白质进行了生物物理预测。为了确定突变蛋白的作用，通过免疫组织化学研究了Gli1和Cli2的表达。结果：在所有四个受影响的成员中，均在外显子4的897C→A处发现了一个新的FTCH1突变。在该家庭的任何未受影响成员或100位无血缘关系的健康中国人中均未发现这种突变。该突变导致PTCH1蛋白的第一个大细胞外环中的氨基酸置换237E→K，这是Sonic Hedgehog（Shh）结合所必需的。这种突变改变了蛋白质的生化特性和蛋白质活性，从而导致Shh / Cli信号通路中转录因子Cli1和Cli2的后续活化。免疫组织化学显示在角化囊性牙源性肿瘤（KCOT）组织中Clil和Cli2过表达。

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