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Codeletion of p15 and p16 in primary malignant mesothelioma
Abstract:
The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in malignant mesothelioma and other cancers. p16 has been implicated recently as a potential target of 9p21 deletions in mesothelioma, but the role of this gene is uncertain because deletions have been detected more often in established cell lines than in primary tumor specimens. We determined p15 and p16 copy number by fluorescence in situ hybridization with a P1 contig in 50 primary mesotheliomas. Codeletion of p15 and p16 was found in 72% of mesotheliomas, including all cases with spindle-cell components (n = 21) and total deletion of p15 and p16 was found in several mesotheliomas that lacked cytogenetic deletion of the chromosome 9 short arm. Point mutations were not found, however, in exon 2 of retained p15 and p16 alleles from seven mesotheliomas. These findings demonstrate that p15, p16 and/or a closely neighboring gene, are the targets of frequent chromosome 9p deletion in primary malignant mesothelioma.
Insights
The p15 and p16 genes are frequently deleted in malignant mesothelioma, indicating their role in cancer development. This study confirms their deletion in primary tumors, implicating them as key targets in mesothelioma pathogenesis.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Malignant mesothelioma is a rare cancer often linked to asbestos exposure.
- The 9p21 chromosomal region, containing p15 and p16 genes, is frequently deleted in various cancers, including mesothelioma.
- The precise role of p16 in mesothelioma is uncertain due to conflicting data from cell lines versus primary tumors.
Purpose of the Study:
- To investigate the copy number of p15 and p16 genes in primary malignant mesothelioma specimens.
- To determine if p15 and p16 deletions are associated with specific mesothelioma subtypes, such as spindle-cell mesothelioma.
- To explore the potential role of p15, p16, or neighboring genes as targets of 9p21 deletions in mesothelioma.
Main Methods:
- Fluorescence in situ hybridization (FISH) was used to determine p15 and p16 gene copy number.
- The study analyzed 50 primary malignant mesothelioma tumor specimens.
- FISH analysis utilized a P1 contig probe specific for the 9p21 region.
Main Results:
- Codeletion of p15 and p16 genes was observed in 72% of primary mesotheliomas.
- All analyzed spindle-cell mesothelioma cases (n=21) exhibited codeletion of p15 and p16.
- Total deletion of p15 and p16 occurred in some mesotheliomas without apparent cytogenetic deletion of chromosome 9p.
- No point mutations were detected in the retained alleles of p15 and p16 in seven examined mesotheliomas.
Conclusions:
- The findings strongly suggest that p15, p16, or closely located genes are frequent targets of deletion at chromosome band 9p21 in primary malignant mesothelioma.
- The high frequency of codeletion, particularly in spindle-cell mesothelioma, highlights the significance of these genetic alterations in tumor development.
- The study underscores the importance of analyzing primary tumor specimens for accurate genetic profiling in mesothelioma research.