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

• DOI: 10.1126/science.271.5247.350
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Stephan A. Hahn; Mieke Schutte; A. T. M. Shamsul ...; Christopher A. Mo...; Luis T. da Costa; Ester Rozenblum; Craig L. Weinstein; Aryeh Fischer; Charles J. Yeo; Ralph H. Hruban; Scott E. Kern
• Keywords: Genetic Markers; 0301 basic medicine; Base Sequence; Molecular Sequence Data; Chromosome Mapping; Gene Expression; Proteins; 3. Good health; DNA-Binding Proteins; Pancreatic Neoplasms; Mice; 03 medical and health sciences; Mutation; Animals; Humans; Genes, Tumor Suppressor; Amino Acid Sequence; Chromosomes, Human, Pair 18; Alleles; Cell Division; Gene Deletion; Neoplasm Transplantation; Signal Transduction

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.