Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis.
Three novel mutations of APC gene in Chinese patients with familial adenomatous polyposis.
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中国家族性腺瘤性息肉病患者 APC 基因的 3 个新突变
DOI：
10.1007/s13277-016-4986-1
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Luo Y
中科院分区：
文献类型：
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作者：
Liu Q;Li X;Li S;Qu S;Wang Y;Tang Q;Ma H;Luo Y
家族性腺瘤性息肉病（FAP）是一种常染色体显性遗传疾病，其特征是发生数百至数千个结肠腺瘤，并增加结直肠癌的风险。大肠腺瘤性息肉病（Adenomatous polyposis coli，APC）是FAP的主要致病基因，它编码一个大的多结构域蛋白，参与拮抗Wnt信号通路。在本研究中，我们通过测序鉴定了5个中国FAP家族APC中的3个新突变和2个复发突变。免疫组织化学分析显示，在这些突变中，一个无义突变（c.2510C G）和两个小缺失（c.2016_2047del，c.3180_3184del）分别导致APC蛋白的截短和β-连环蛋白在受影响个体的结直肠样本中的胞质和核积聚。我们的研究扩大了APC突变的数据库，并为理解APC在FAP中的功能提供了证据。
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder characterized by the development of hundreds to thousands of colonic adenomas and an increased risk of colorectal cancer. Adenomatous polyposis coli (APC), encoding a large multidomain protein involved in antagonizing the Wnt signaling pathway, has been identified as the main causative gene responsible for FAP. In this study, we identified three novel mutations as well as two recurrent mutations in the APC in five Chinese FAP families by sequencing. Immunohistochemical analysis revealed that among these mutations, a nonsense mutation (c.2510C>G) and two small deletions (c.2016_2047del, c.3180_3184del) led to the truncation of the APC protein and the cytoplasmic and nuclear accumulation of β-catenin in the colorectal samples from affected individuals, respectively. Our study expands the database on mutations of APC and provides evidence to understand the function of APC in FAP.