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p27/Kip1 mutation found in breast cancer
K S Spirin1, J F Simpson, S Takeuchi
1Department of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California 90048, USA.
Cancer Research
|May 15, 1996
Summary
Mutations in the p27/Kip1 protein, a cell cycle regulator, are rare in breast cancer but can contribute to tumor development. Loss of heterozygosity at chromosome 12p13 suggests other tumor suppressor genes are involved.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p27/Kip1 protein is a cyclin-dependent kinase inhibitor involved in cell cycle regulation.
- Cyclin-dependent kinase inhibitors can suppress cell proliferation, suggesting a role as tumor suppressor genes.
Purpose of the Study:
- To investigate alterations in the p27 gene in breast cancer.
- To determine if p27 mutations contribute to tumorigenesis.
Main Methods:
- Analysis of 36 primary breast carcinomas and 9 cell lines.
- Techniques included PCR-single-strand conformational polymorphism, DNA sequencing, and Southern blot analysis.
- Loss of heterozygosity (LOH) analysis at chromosome 12p13 was performed.
Main Results:
- No homozygous deletions of the p27 gene were found.
- Two point mutations were identified in primary tumors, including a nonsense mutation at codon 104.
- The nonsense mutation was associated with LOH at 12p13.
- Four additional samples showed LOH at 12p13 without p27 gene alteration.
Conclusions:
- p27 mutations are infrequent in breast cancer but can be significant in a subset of cases.
- LOH at 12p13 suggests the presence of another tumor suppressor gene on chromosome 12p involved in breast cancer pathogenesis.