Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Membrane / metabolism
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Cell Nucleus / metabolism
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Chromosome Mapping
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Chromosomes, Human, Pair 18
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Colorectal Neoplasms / genetics*
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DNA-Binding Proteins*
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Female
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Frameshift Mutation
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Gastrointestinal Neoplasms / genetics*
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Genes, DCC
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Genes, Tumor Suppressor*
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Genetic Predisposition to Disease
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Germ-Line Mutation
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Hamartoma Syndrome, Multiple / genetics*
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Humans
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Intestinal Polyps / genetics*
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Male
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Pedigree
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Polymerase Chain Reaction
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Sequence Deletion
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Signal Transduction
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Smad4 Protein
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Trans-Activators / chemistry
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Trans-Activators / genetics*
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Trans-Activators / metabolism
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Transforming Growth Factor beta / metabolism
Substances
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DNA-Binding Proteins
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SMAD4 protein, human
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Smad4 Protein
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Trans-Activators
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Transforming Growth Factor beta