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p16INK4/p15INK4B gene inactivation is a frequent event in malignant T-cell lines
L Borgonovo Brandter1, M Heyman, O Rasool
1Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Abstract:
The cell cycle regulators p16INK4 and p15INK4B have been mapped to the minimal region of overlap for chromosome 9p21 deletions, observed in a number of malignancies, suggesting that they could be tumor suppressor genes (TSGs). In the case of p16INK4 this has been further substantiated by the finding of small intragenic mutations. In this study we have investigated the p16INK4 and p15INK4B genes in 16 malignant T-cell lines by means of Southern blot, PCR and sequence analysis. p16INK4 allelic deletions occurred in 15 of 16 cell lines; 12 of which were homozygous and 3 hemizygous. In 1 cell line (DND 41) the remaining p16INK4 allele carried a microdeletion of 29 bp of exon 2, supporting the concept that p16INK4 is a target TSG for deletions on 9p21. Most p16INK4 deletions also included the p15INK4B gene. However, 4 of the cell lines deleted for p16INK4 showed no evidence of p15INK4B loss, indicating that p15INK4B is not the target in these cell lines.
Insights
The p16INK4 gene is frequently deleted in T-cell malignancies, supporting its role as a tumor suppressor gene. While p15INK4B is often co-deleted, it is not the sole target in all cases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome 9p21 deletions are common in malignancies.
- The cell cycle regulators p16INK4 and p15INK4B are located in this region.
- These genes are suspected tumor suppressor genes (TSGs).
Purpose of the Study:
- To investigate the p16INK4 and p15INK4B genes in 16 malignant T-cell lines.
- To determine if p16INK4 and p15INK4B act as tumor suppressor genes in T-cell malignancies.
Main Methods:
- Southern blot analysis
- Polymerase chain reaction (PCR)
- Sequence analysis
Main Results:
- p16INK4 allelic deletions were observed in 15 out of 16 T-cell lines (12 homozygous, 3 hemizygous).
- A microdeletion in exon 2 of the remaining p16INK4 allele was found in one cell line (DND 41).
- Most p16INK4 deletions also involved the p15INK4B gene, but 4 cell lines showed p15INK4B loss without p16INK4 deletion.
Conclusions:
- p16INK4 is a likely target tumor suppressor gene for deletions on chromosome 9p21.
- p15INK4B is not the sole target TSG in all cases of 9p21 deletions, as evidenced by differential deletion patterns.