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Tumor-suppressive pathways in pancreatic carcinoma
E Rozenblum1, M Schutte, M Goggins
1Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA.
Cancer Research
|May 1, 1997
Summary
Genetic analysis of pancreatic adenocarcinomas reveals frequent mutations in K-ras, p16, p53, and DPC4. Concordant inactivation of p16 and DPC4 suggests a sequential mutation advantage in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumorigenesis involves positive selection of cells altering rate-limiting pathways.
- Mutations in different genes within a tumor suggest involvement in distinct tumor-suppressive pathways.
Purpose of the Study:
- To investigate genetic alterations in K-ras, p16, p53, and DPC4 in pancreatic adenocarcinomas.
- To understand the interplay and significance of these genetic alterations in human tumorigenesis.
Main Methods:
- Studied genetic alterations in K-ras, p16, p53, and DPC4 in 42 pancreatic adenocarcinomas.
- Performed multigenic analysis to identify co-occurring mutations and their frequencies.
Main Results:
- All 42 tumors exhibited K-ras gene mutations.
- 38% of tumors had four altered genes, 38% had three, 15% had two, and 8% had one.
- A significant concordance was observed between DPC4 and p16 inactivation (P = 0.007).
Conclusions:
- K-ras mutation is a near-universal event in pancreatic adenocarcinoma.
- The high concordance of DPC4 and p16 inactivation suggests a selective advantage for DPC4 mutation following p16 inactivation.
- Multigenic analysis aids in understanding critical tumor-suppressive pathways in human tumorigenesis.