Mutations in the SMAD4/DPC4 gene in juvenile polyposis.

Journal article

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.

Authors: Howe, JR; Roth, S; Ringold, J; Summers, R; Järvinen, H

• Publication status: Published
• Journal: Science (New York, N.Y.)
• Volume: 280
• Issue: 5366
• Pages: 1086-1088
• Publication date: 1998-05-01
• DOI: 10.1126/science.280.5366.1086
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Smad4 Protein; Cell Nucleus; Hamartoma Syndrome, Multiple; Genetic Predisposition to Disease; Cell Membrane; Germ-Line Mutation; Gastrointestinal Neoplasms; Male; Genes, DCC; Intestinal Polyps; Pedigree; DNA-Binding Proteins; Polymerase Chain Reaction; Colorectal Neoplasms; Chromosomes, Human, Pair 18; Transforming Growth Factor beta; Female; Genes, Tumor Suppressor; Chromosome Mapping; Signal Transduction; Humans; Frameshift Mutation; Sequence Deletion; Trans-Activators