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p16 (CDKN2) is a major deletion target at 9p21 in bladder cancer
M P Williamson1, P A Elder, M E Shaw
1Molecular Genetics Laboratory, Marie Curie Research Institute, Oxted, Surrey, UK.
Abstract:
The p16 gene has been identified as a candidate tumour suppressor gene at 9p21, a region commonly deleted in bladder cancer. We screened 140 bladder tumours and 16 cell lines for deletions and sequence variants of p16. Eight cell lines showed homozygous deletion of p16 and two had small sequence variations. All 13 tumours with small defined deletions of 9p21, 18/31 (58%) of tumours with monosomy 9 and 9/91 (10%) of tumours with no chromosome 9 loss of heterozygosity had homozygous deletion of p16. No tumour-specific sequence variants were identified. Deletion mapping revealed a nested set of deletions focused on p16. Six deletions involved p16 but not the related and adjacent gene p15 and one tumour had an intragenic deletion of p16. All other deletions involved both p16 and p15. We conclude that p16 represents the major target for deletion at 9p21 in bladder cancer.
Insights
The p16 gene, a tumor suppressor, is frequently deleted in bladder cancer. Our study confirms p16 is the primary target for deletions at chromosome 9p21 in these tumors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The 9p21 chromosomal region is frequently altered in bladder cancer.
- The p16 gene is a candidate tumor suppressor located at 9p21.
Purpose of the Study:
- To investigate deletions and sequence variants of the p16 gene in bladder cancer.
- To determine if p16 is the primary target of deletions at 9p21.
Main Methods:
- Screening of 140 bladder tumors and 16 cell lines for p16 alterations.
- Deletion mapping and analysis of sequence variants.
- Assessing p16 status in relation to chromosomal abnormalities of chromosome 9.
Main Results:
- Eight cell lines exhibited homozygous deletion of p16; two had sequence variations.
- Homozygous deletion of p16 was found in 100% of tumors with 9p21 deletions, 58% with monosomy 9, and 10% with no LOH on chromosome 9.
- No tumor-specific sequence variants of p16 were identified.
- Deletion mapping indicated p16 as the central focus, with some deletions affecting p15 as well.
Conclusions:
- p16 is the major target for deletion at the 9p21 locus in bladder cancer.
- The genetic alterations of p16 play a significant role in bladder tumorigenesis.