Mutations in the SMAD4/DPC4 gene in juvenile polyposis.
Howe JR., Roth S., Ringold JC., Summers RW., Järvinen HJ., Sistonen P., Tomlinson IP., Houlston RS., Bevan S., Mitros FA., Stone EM., Aaltonen LA.
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.