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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alleles
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Cell Division
-
Chromosome Mapping
-
Chromosomes, Human, Pair 18*
-
DNA-Binding Proteins*
-
Gene Deletion
-
Gene Expression
-
Genes, Tumor Suppressor*
-
Genetic Markers
-
Humans
-
Mice
-
Molecular Sequence Data
-
Mutation
-
Neoplasm Transplantation
-
Pancreatic Neoplasms / genetics*
-
Pancreatic Neoplasms / pathology
-
Proteins / chemistry
-
Proteins / genetics*
-
Proteins / physiology
-
Signal Transduction
-
Smad4 Protein
-
Trans-Activators*
-
Transforming Growth Factor beta / physiology
-
Transplantation, Heterologous
-
Tumor Cells, Cultured
Substances
-
DNA-Binding Proteins
-
Genetic Markers
-
Proteins
-
SMAD4 protein, human
-
Smad4 Protein
-
Smad4 protein, mouse
-
Trans-Activators
-
Transforming Growth Factor beta
Associated data
-
GENBANK/AF045438
-
GENBANK/AF045439
-
GENBANK/AF045440
-
GENBANK/AF045441
-
GENBANK/AF045442
-
GENBANK/AF045443
-
GENBANK/AF045444
-
GENBANK/AF045445
-
GENBANK/AF045446
-
GENBANK/AF045447
-
GENBANK/U44378