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Mutations of the DPC4/Smad4 Gene in Biliary Tract Carcinoma¹

Department of Internal Medicine, University of Bochum, 44892 Bochum, [S. A. H., A. S., H. G., M. B., I. S-W., W. S.]; Departments of Surgery [D. B.] and Pathology [A. R.], University of Marburg, 35043 Marburg; and Department of Pathology, University of Mainz, 55101 Mainz [H. M.], Germany

A candidate tumor suppressor gene, DPC4, located at 18q21.1, has recently been shown to be inactivated in half of pancreatic adenocarcinomas. The close developmental relationship of the pancreas and biliary tract prompted us to determine the role of DPC4 in the multistep carcinogenesis of biliary tract carcinoma. A search for mutations in the genomic sequence of the highly conserved COOH-terminal domain of DPC4 (exons 8–11) was performed by single-strand conformational polymorphism analysis. Five of 32 (16%) primary biliary tract carcinomas had point mutations in the DPC4 sequence. Interestingly, inactivation of DPC4 was especially common in carcinomas originating from the common bile duct (four of eight specimens analyzed), suggesting an important role for DPC4 in the development of this subtype of biliary tract tumor.

¹ This work was supported by grants from the Deutsche Krebshilfe (to S. A. H., I. S-W., and W. S.) and from the Ruhr-Universität-Bochum (FORUM; to S. A. H. and I. S-W.), and by Grant Ba 1467/2-1 from the Deutsche Forschungsgemeinschaft (to D. B.).

² To whom requests for reprints should be addressed, at Department of Internal Medicine, University of Bochum, In der Schornau 23–25, 44892 Bochum, Germany. Phone: (49) 234 299 3401; Fax: (49) 234 299 3409.

Received 11/12/97. Accepted 1/19/98.

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