TP53 Deletion Probe

Although previously difficult to detect, the advent of FISH analysis of interphase cells of patients with B-CLL showed that around 17% of patients with the disease have deletions of the TP53 gene. As with ATM, deletions of TP53 have important therapeutic implications to patients with B-CLL. Knowledge of the deletion status of TP53 in the patient should mediate the choice of therapy. The TP53 gene is a tumour suppressor gene and its product, the p53 protein, is responsible for the death of DNA damaged cells and is thought to be brought about through its phosphorylation and subsequent removal of its inhibition by MDM2 (Mouse Double Minute 2 Homolog). This phosphorylation is mediated by ATM. In the absence of TP53 activity, cells that cannot be repaired by ATM will continue to proliferate in their damaged state. Patients deleted for TP53 may be rendered resistant to alkylating chemotherapeutic agents as these are designed to damage the DNA in the cells that TP53 would have destroyed. In the absence of TP53, therefore, patients treated with these agents will harbour a proliferating population of damaged cells.

The TP53 probe is 83 kb, labelled in red and covers a region including 15 kb of the 5’ end of TP53 and extending 67 kb proximal to the gene to just beyond the marker D17S655. The probe mix also contains a control probe for the 17 centromere (D17Z1).