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p16 mutations/deletions are not frequent events in prostate cancer
Y Tamimi1, P P Bringuier, F Smit
1Department of Urology/Urological Research Laboratory, University Hospital Nijmegen, The Netherlands.
Abstract:
Cyclin-dependent kinase-4 inhibitor gene (p16INK4) has recently been mapped to chromosome 9p21. Homozygous deletions of this gene have been found at high frequency in cell lines derived from different types of tumours. These findings suggested therefore, that p16INK4 is a tumour-suppressor gene involved in a wide variety of human cancers. To investigate the frequency of p16INK mutations/deletions in prostate cancer, we screened 20 primary prostate tumours and four established cell lines by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis for exon 1 and exon 2. In contrast to most previous reports, no homozygous deletions were found in prostate cancer cell lines, but one cell line (DU145) has revealed to a mutation at codon 76. Only two SSCP shifts were detected in primary tumours: one of them corresponds to a mutation at codon 55 and the other one probably corresponds to a polymorphism. These data suggest that mutation of the p16INK4 gene is not a frequent genetic alteration implicated in prostate cancer development.
Insights
Mutations in the p16INK4 gene are uncommon in prostate cancer. This study found no homozygous deletions in cell lines and rare mutations in primary tumors, suggesting p16INK4 is not a frequent cause of prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The cyclin-dependent kinase-4 inhibitor gene (p16INK4), located on chromosome 9p21, is recognized as a tumor-suppressor gene.
- High frequencies of homozygous deletions in p16INK4 have been observed in various tumor-derived cell lines, implicating it in diverse human cancers.
Purpose of the Study:
- To determine the frequency of p16INK4 gene mutations and deletions in prostate cancer.
- To investigate the role of p16INK4 alterations in the development of prostate cancer.
Main Methods:
- Screening of 20 primary prostate tumors and four established cell lines.
- Utilized polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis for exons 1 and 2 of the p16INK4 gene.
Main Results:
- No homozygous deletions of p16INK4 were detected in the examined prostate cancer cell lines, contrary to previous reports.
- One prostate cancer cell line (DU145) exhibited a mutation at codon 76.
- Two instances of SSCP shifts were identified in primary tumors, with one indicating a mutation at codon 55 and the other likely representing a polymorphism.
Conclusions:
- Alterations in the p16INK4 gene, including mutations and deletions, do not appear to be a frequent genetic event in prostate cancer development.
- The findings suggest that p16INK4 is unlikely to be a primary driver in a significant proportion of prostate cancers.