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PMID: 9582123 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mutations in the SMAD4/DPC4 gene in juvenile polyposis.

Science (New York, N.Y.) ·Vol. 280 ·No. 5366 ·1998-05-15 ·Pages 1086-8

Howe JR, Roth S, Ringold JC, Summers RW, Järvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA

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.

MeSH Terms

Cell Membrane/metabolism Cell Nucleus/metabolism Chromosome Mapping Chromosomes, Human, Pair 18 Colorectal Neoplasms/genetics DNA-Binding Proteins Female Frameshift Mutation Gastrointestinal Neoplasms/genetics Genes, DCC Genes, Tumor Suppressor Genetic Predisposition to Disease Germ-Line Mutation Hamartoma Syndrome, Multiple/genetics Humans Intestinal Polyps/genetics Male Pedigree Polymerase Chain Reaction Sequence Deletion Signal Transduction Smad4 Protein Trans-Activators/chemistry,genetics,metabolism Transforming Growth Factor beta/metabolism

Chemicals

DNA-Binding Proteins SMAD4 protein, human Smad4 Protein Trans-Activators Transforming Growth Factor beta

Authors & Affiliations

12 authors, click to expand affiliations / ORCID

Howe J R

Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA. [email protected]

Roth S

Ringold J C

Summers R W

Järvinen H J

Sistonen P

Tomlinson I P

Houlston R S

Bevan S

Mitros F A

Stone E M

Aaltonen L A

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.280.5366.1086

[email protected]

Published

1998-05-15

Pages

1086-8

Language

English

Region

United States

NLM ID

0404511

Subset

Corrections

CommentIn

PMID: 9616081

External Links

PubMed source DOI: 10.1126/science.280.5366.1086 View journal details

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Mutations in the SMAD4/DPC4 gene in juvenile polyposis.

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