title: DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
abstract: 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-beta (TGF-beta)-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.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Hahn
authors.forename: M
authors.initials: M
authors.lastname: Schutte
authors.forename: A T
authors.initials: AT
authors.lastname: Hoque
authors.forename: C A
authors.initials: CA
authors.lastname: Moskaluk
authors.forename: L T
authors.initials: LT
authors.lastname: da Costa
authors.forename: E
authors.initials: E
authors.lastname: Rozenblum
authors.forename: C L
authors.initials: CL
authors.lastname: Weinstein
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: C J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: S E
authors.initials: SE
authors.lastname: Kern
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011506:Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta