DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1

American Association for the Advancement of Science (AAAS) - Tập 271 Số 5247 - Trang 350-353 - 1996
Stephan A. Hahn1, Mieke Schutte1, A.T.M. Shamsul Hoque1, Christopher A. Moskaluk1, Luís Teixeira da Costa2, Ester Rozenblum1, Craig L. Weinstein1, Aryeh Fischer1, Charles J. Yeo3, Ralph H. Hruban1, Scott E. Kern4
1S. A. Hahn, M. Schutte, A. T. M. S. Hoque, C. A. Moskaluk, E. Rozenblum, C. L. Weinstein, A. Fischer, R. H. Hruban, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2L. T. da Costa, Graduate Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3C. J. Yeo, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4S. E. Kern, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Tóm tắt

About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4 , a gene similar in sequence to a Drosophila melanogaster gene ( Mad ) implicated in a transforming growth factor-β (TGF-β)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.

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