The P53 probe is 161kb, labelled in red, covers the whole P53 (TP53) gene, extending 66kb telomeric to the gene and covering a region centromeric to the gene, to just beyond the marker D17S655. The probe mix also contains a control probe for the 17 centromere (D17Z1) labelled in green.
Although previously difficult to detect, the advent of FISH analysis of interphase cells from patients with B-CLL showed that around 17% of patients with the disease have deletions of the P53 (TP53) gene1. As with ATM, deletions of P53 have important therapeutic implications for patients with B-CLL2.
Knowledge of the P53 deletion status in the patient should mediate the choice of therapy3. P53 is a tumour suppressor gene and its protein product is responsible for the death of cells that contain damaged DNA. This is thought to be brought about by phosphorylation of P53 and the subsequent prevention of its repression by MDM2 (Mouse Double Minute 2 Homolog). This phosphorylation is mediated by ATM. In the absence of P53 activity, cells that cannot be repaired by ATM will continue to proliferate in their damaged state. Patients deleted for P53 may be rendered resistant to alkylating chemotherapeutic agents3 and purine analogues4 as these are designed to damage DNA in the cells that P53 would have destroyed. In the absence of P53, therefore, patients treated with these agents will harbour a proliferating population of damaged cells.
The quality and reproducibility of results using the CytoCell kit has been vital in accurately detecting co-deletions in our glioma investigations. We now have a cost-effective test that we can rely on that is also easy to use and interpret. We've been consistently impressed with this kit - not to mention the support offered by OGT's customer service, and have completely transitioned over to CytoCell probes.
Gavin Cuthbert, FRCPath
Head of Cancer Cytogenetics, Northern Genetics Service, Newcastle, UK