Publication Date:
1998-06-06
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, J R -- Roth, S -- Ringold, J C -- Summers, R W -- Jarvinen, H J -- Sistonen, P -- Tomlinson, I P -- Houlston, R S -- Bevan, S -- Mitros, F A -- Stone, E M -- Aaltonen, L A -- New York, N.Y. -- Science. 1998 May 15;280(5366):1086-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA. james-howe@uiowa.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9582123" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
