DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
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.
Hahn
S A
SA
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Schutte
M
M
Hoque
A T
AT
Moskaluk
C A
CA
da Costa
L T
LT
Rozenblum
E
E
Weinstein
C L
CL
Fischer
A
A
Yeo
C J
CJ
Hruban
R H
RH
Kern
S E
SE
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
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