Related Experiment Videos
Germline mutations of the dpc4 gene in Korean juvenile polyposis patients
1Korean Hereditary Tumor Registry, Laboratory of Cell Biology, Cancer Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Insights
Germline mutations in the dpc4 (deleted in pancreatic carcinoma, locus 4) gene are linked to juvenile polyposis, a rare childhood condition. This study identified dpc4 gene alterations in 3 of 5 patients, confirming its role in the disease.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- Juvenile polyposis is a rare, autosomal dominant condition characterized by multiple gastrointestinal polyps, primarily in children.
- The deleted in pancreatic carcinoma, locus 4 (dpc4/SMAD4) gene is a candidate tumor suppressor implicated in juvenile polyposis.
- The dpc4 gene is involved in the transforming growth factor-beta (TGF-beta) signaling pathway.
Purpose of the Study:
- To investigate the role of dpc4 gene alterations in the development of juvenile polyposis.
- To screen Korean juvenile polyposis patients for mutations in the dpc4 gene.
Main Methods:
- Screening of 5 Korean juvenile polyposis patients using Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) analysis.
- Bi-directional sequencing of the dpc4 gene to identify mutations.
- Analysis of germline mutations in exons 8 and 9 of the dpc4 gene.
Main Results:
- Germline mutations in the dpc4 gene were identified in 3 out of 5 patients.
- Two patients had genetic alterations in exon 9, and one patient had a mutation in exon 8.
- Identified mutations included a nonsense mutation and two missense mutations within the C-terminus of the dpc4 gene.
Conclusions:
- Alterations in the dpc4 gene are a cause of juvenile polyposis.
- The identified mutations in the dpc4 gene provide further evidence for its role as a tumor suppressor in juvenile polyposis.
- These findings highlight the importance of genetic screening for dpc4 mutations in patients diagnosed with juvenile polyposis.
Abstract:
Juvenile polyposis is an uncommon condition characterized by the development of multiple (usually more than 5) juvenile polyps in the gastrointestinal tract, especially in the colon. This disease usually occurs during childhood, and is inherited in an autosomal dominant fashion. It has been suggested that the dpc4 (deleted in pancreatic carcinoma, locus 4) gene, which is located on chromosome 18q21.1, might cause juvenile polyposis. The dpc4 (smad4) gene is a candidate tumor-suppressor gene and may play a role in the TGF-beta-signaling pathway. To confirm the idea that alterations of the dpc4 gene may result in juvenile polyposis, we screened 5 Korean juvenile-polyposis patients by PCR-SSCP (single-strand conformation polymorphism) analysis and bi-directional sequencing. There were germline mutations of the dpc4 gene in 3 out of the 5 patients: 2 had a genetic alteration in exon 9 and the third had a mutation in exon 8. These germline mutations occurred in the C-terminus of the dpc4 gene, similar to most published mutations. One patient exhibited a non-sense mutation (codon 388), which changed a glutamine codon (CAG) to a stop codon (TAG). The second patient harbored a mis-sense mutation (codon 390), causing a non-conservative amino-acid change