Mutations in the SMAD4/DPC4 gene in juvenile polyposis

James R Howe; Stina Roth; John C Ringold; Robert W Summers; Heikki J Järvinen; Pertti Sistonen; Ian P M Tomlinson; Richard S Houlston; Steve Bevan; Frank A Mitros; Edwin M Stone; Lauri A Aaltonen

doi:10.1126/science.280.5366.1086

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Mutations in the SMAD4/DPC4 gene in juvenile polyposis

Journal article

Peer reviewed

Mutations in the SMAD4/DPC4 gene in juvenile polyposis

James R Howe, Stina Roth, John C Ringold, Robert W Summers, Heikki J Järvinen, Pertti Sistonen, Ian P M Tomlinson, Richard S Houlston, Steve Bevan, Frank A Mitros, …

Science (American Association for the Advancement of Science), Vol.280(5366), pp.1086-1088

05/15/1998

DOI: 10.1126/science.280.5366.1086

PMID: 9582123

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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.

Polymerase Chain Reaction

Signal Transduction

Sequence Deletion

Frameshift Mutation

Gastrointestinal Neoplasms - genetics

Colorectal Neoplasms - genetics

Humans

Male

Trans-Activators - chemistry

Intestinal Polyps - genetics

Cell Nucleus - metabolism

Trans-Activators - genetics

Germ-Line Mutation

Female

Cell Membrane - metabolism

Genes, Tumor Suppressor

DNA-Binding Proteins

Genetic Predisposition to Disease

Hamartoma Syndrome, Multiple - genetics

Chromosome Mapping

Smad4 Protein

Chromosomes, Human, Pair 18

Pedigree

Trans-Activators - metabolism

Transforming Growth Factor beta - metabolism

Genes, DCC

Details

Title: Subtitle: Mutations in the SMAD4/DPC4 gene in juvenile polyposis
Creators: James R Howe - Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA. james-howe@uiowa.edu
Stina Roth
John C Ringold
Robert W Summers
Heikki J Järvinen
Pertti Sistonen
Ian P M Tomlinson
Richard S Houlston
Steve Bevan
Frank A Mitros
Edwin M Stone
Lauri A Aaltonen
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.280(5366), pp.1086-1088
DOI: 10.1126/science.280.5366.1086
PMID: 9582123
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Publisher: United States
Language: English
Date published: 05/15/1998
Academic Unit: Pathology; Iowa Neuroscience Institute; Surgery; Ophthalmology and Visual Sciences
Record Identifier: 9983980032602771

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