DPC4, A CANDIDATE TUMOR-SUPPRESSOR GENE AT HUMAN-CHROMOSOME 18Q21.1

About 90 percent of human pancreatic carcinomas show allelic loss at c hromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of h omboygous 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-beta (TGF-beta)-like signaling pathway. Potentially inactivati ng mutations in DPC4 were identified in six of 27 pancreatic carcinoma s that did not have homozygous deletions at 18q21.1. These results ide ntify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.