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Analysis of the DPC4 gene in gastric carcinoma
S Nishizuka1, G Tamura, C Maesawa
1Department of Pathology, Iwate Medical University School of Medicine, Morioka.
Abstract:
Allelic loss on chromosome 18q is involved in the progression of gastric carcinoma. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate tumor suppressor gene, has been localized at 18q21.1. This gene is inactivated in nearly one half of pancreatic carcinomas. We tested for DPC4 gene mutations and allelic status at 18q21 in 30 primary gastric carcinomas and 5 gastric carcinoma cell lines. Polymerase chain reaction single-strand conformation polymorphism and sequencing analyses revealed no DPC4 mutations in any of the primary tumors or cell lines. Homozygous deletion of DPC4 was observed in only 1 (MKN-45) of the 5 (20%) cell lines. This suggests that the target gene for loss on 18q is not DPC4. The true tumor suppressor gene, encoded near DPC4, has yet to be identified.
Insights
Allelic loss on chromosome 18q is implicated in gastric cancer progression. This study found no DPC4 gene mutations in gastric tumors, suggesting DPC4 is not the primary tumor suppressor gene involved in 18q loss.
Area of Science:
- Oncology
- Molecular Genetics
- Cancer Biology
Background:
- Allelic loss on chromosome 18q is a known factor in gastric carcinoma progression.
- The DPC4 (deleted in pancreatic carcinoma, locus 4) gene, located at 18q21.1, is a candidate tumor suppressor gene previously inactivated in pancreatic cancers.
Purpose of the Study:
- To investigate the role of the DPC4 gene in gastric carcinoma by examining mutations and allelic status at 18q21.
- To determine if DPC4 is the target tumor suppressor gene responsible for 18q allelic loss in gastric cancer.
Main Methods:
- Analysis of DPC4 gene mutations and allelic status in 30 primary gastric carcinomas and 5 gastric carcinoma cell lines.
- Utilized polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and sequencing techniques.
Main Results:
- No DPC4 gene mutations were detected in any of the analyzed primary gastric tumors or cell lines.
- Homozygous deletion of the DPC4 gene was found in only one out of five (20%) gastric carcinoma cell lines (MKN-45).
Conclusions:
- The findings suggest that DPC4 is unlikely to be the primary tumor suppressor gene targeted by 18q allelic loss in gastric carcinoma.
- The actual tumor suppressor gene responsible for 18q loss in gastric cancer remains to be identified, but it is likely located near DPC4.