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Science 15 May 1998:
Vol. 280. no. 5366, pp. 1086 - 1088
DOI: 10.1126/science.280.5366.1086
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Reports

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

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.

J. R. Howe and J. C. Ringold, Department of Surgery, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
S. Roth and L. A. Aaltonen, Department of Medical Genetics, Haartman Institute, FIN-00014, University of Helsinki, Finland.
R. W. Summers, Department of Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
H. J. Järvinen, Second Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland.
P. Sistonen, Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, 00130 Helsinki, Finland.
I. P. M. Tomlinson, Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln's Inn Fields, London, WC2A 3PX, UK.
R. S. Houlston and S. Bevan, Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
F. A. Mitros, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
E. M. Stone, Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
*   To whom correspondences should be addressed. E-mail: james-howe{at}uiowa.edu

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Intracellular Signaling of the TGF-{beta} Superfamily by Smad Proteins.
M. KAWABATA, T. IMAMURA, H. INOUE, J.-I. HANAI, A. NISHIHARA, A. HANYU, M. TAKASE, Y. ISHIDOU, Y. UDAGAWA, E. OEDA, et al. (1999)
Ann. N.Y. Acad. Sci. 886, 73-82