Mutations in the SMAD4/DPC4 gene in juvenile polyposis
Mutations in the SMAD4/DPC4 gene in juvenile polyposis
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DOI：
10.1126/science.280.5366.1086
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发表时间：
1998-05-15
期刊：
影响因子：
56.9
通讯作者：
Aaltonen, LA
中科院分区：
文献类型：
--
作者：
Howe, JR;Roth, S;Aaltonen, LA
家族性幼年性息肉病是一种常染色体显性遗传疾病，其特征是易患错构瘤性息肉和胃肠癌。在这里，它表明，青少年息肉病家族的一个子集携带位于染色体18q21.1上的基因SMAD 4（也称为DPC 4）的生殖系突变，该基因编码转化生长因子β信号通路中的关键细胞质介质。预测突变SMAD4蛋白在羧基末端被截短，并且缺乏正常功能所需的序列。这些结果证实了SMAD4在胃肠道肿瘤发展中的重要作用。
Familial juvenile polyposis is an autosomal dominant disease characterized by a predisposition to hamartomatous polyps and gastrointestinal cancer. Here it is shown that a subset of juvenile polyposis families carry germ line mutations in the gene SMAD4 (also known as DPC4), located on chromosome 18q21.1, that encodes a critical cytoplasmic mediator in the transforming growth factor-beta signaling pathway. The mutant SMAD4 proteins are predicted to be truncated at the carboxyl-terminus and lack sequences required for normal function. These results confirm an important role for SMAD4 in the development of gastrointestinal tumors.