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Somatic mutations of the WAF1/CIP1 gene in primary prostate cancer
1Department of Radiation Oncology [Cancer Biology Division], Wayne State University School of Medicine, Detroit, Michigan 48202, USA.
Abstract:
The WAF1/CIP1 gene, a potential tumor suppressor gene, has recently been cloned and identified as a p53 mediator and an inhibitor for G1 cyclin-dependent kinases (CDKs). We undertook this study to investigate the possible role of the WAF1/CIP1 gene in human prostatic carcinoma. Matched normal and cancer tissues from 18 patients with prostate cancer were screened for WAF1/CIP1 mutation by nested reverse transcription-polymerase chain reaction/single strand conformational polymorphism (RT-PCR/SSCP) and DNA sequencing. Shifted bands from three tumor, but not the matched normal specimens, were observed. Subsequent direct DNA sequencing of the PCR fragments identified four sequence alterations including a cytosine (C) to adenine (A) transversion and a guanine (G) to A transition and two A insertions. Our results demonstrated that mutations of the WAF1/CIP1 gene occur and may be important during the pathogenesis of human prostate cancer. This is the first report of WAF1/CIP1 mutation in a primary human cancer.
Insights
Mutations in the WAF1/CIP1 gene, a key cell cycle regulator, were found in human prostate cancer tissues. These WAF1/CIP1 gene alterations may play a role in the development of prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The WAF1/CIP1 gene is recognized as a potential tumor suppressor.
- It functions as a p53 mediator and inhibits G1 cyclin-dependent kinases (CDKs).
Purpose of the Study:
- To investigate the potential role of WAF1/CIP1 gene mutations in human prostate cancer development.
- To screen for WAF1/CIP1 gene alterations in primary prostate tumors.
Main Methods:
- Nested reverse transcription-polymerase chain reaction/single strand conformational polymorphism (RT-PCR/SSCP) was used to screen for mutations.
- DNA sequencing was performed on identified altered bands from tumor and normal tissue samples.
Main Results:
- Sequence alterations in the WAF1/CIP1 gene were detected in three out of 18 prostate cancer specimens.
- Four specific sequence alterations were identified, including base substitutions and insertions.
- No mutations were found in the matched normal prostate tissues.
Conclusions:
- WAF1/CIP1 gene mutations occur in human prostate cancer.
- These mutations may be significant in the pathogenesis of prostate cancer.
- This study represents the first report of WAF1/CIP1 mutations in primary human cancer.