title: Mutations in the SMAD4/DPC4 gene in juvenile polyposis.
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.
authors.affiliation: Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA. james-howe@uiowa.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Howe
authors.forename: S
authors.initials: S
authors.lastname: Roth
authors.forename: J C
authors.initials: JC
authors.lastname: Ringold
authors.forename: R W
authors.initials: RW
authors.lastname: Summers
authors.forename: H J
authors.initials: HJ
authors.lastname: Järvinen
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: I P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: F A
authors.initials: FA
authors.lastname: Mitros
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D016368:Frameshift Mutation; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D016163:Genes, DCC; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics*; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D015398:Signal Transduction; D051901:Smad4 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta