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Frequency of homozygous deletion at p16/CDKN2 in primary human tumours
P Cairns1, T J Polascik, Y Eby
1Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Abstract:
Many tumour types have been reported to have deletion of 9p21 (refs 1-6). A candidate target suppressor gene, p16 (p16INK4a/MTS-1/CDKN2), was recently identified within the commonly deleted region in tumour cell lines. An increasing and sometimes conflicting body of data has accumulated regarding the frequency of homozygous deletion and the importance of p16 in primary tumours. We tested 545 primary tumours by microsatellite analysis with existing and newly cloned markers around the p16 locus. We have now found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer. Moreover, fine mapping of these deletions implicates a 170 kb minimal region that includes p16 and excludes p15.
Insights
Small homozygous deletions at 9p21 are common in bladder, breast, and prostate cancers. This inactivation mechanism primarily involves the p16 gene, crucial for tumor suppression.
Area of Science:
- Oncology
- Cancer Genetics
Background:
- Deletion of 9p21 is observed in various tumor types.
- The p16 (p16INK4a/MTS-1/CDKN2) gene, a candidate tumor suppressor, is located in the 9p21 region.
- Conflicting data exists on the frequency and significance of p16 homozygous deletion in primary tumors.
Purpose of the Study:
- To investigate the frequency and mechanism of 9p21 deletions in primary tumors.
- To determine the role of the p16 gene in tumor development.
Main Methods:
- Microsatellite analysis was performed on 545 primary tumors.
- Analysis utilized existing and newly developed markers around the p16 locus.
- Fine mapping was employed to delineate deletion regions.
Main Results:
- Small homozygous deletions are the predominant mechanism of 9p21 inactivation in bladder tumors.
- These deletions were also found in breast and prostate cancers.
- Fine mapping identified a 170 kb minimal region including p16 but excluding p15.
Conclusions:
- Homozygous deletion of p16 is a significant mechanism for tumor development in bladder, breast, and prostate cancers.
- The findings clarify the role of p16 in 9p21 tumor suppressor gene inactivation.
- A precise minimal deletion region implicating p16 has been defined.