P16 Deletion Probe

Deletions of chromosome 9p21 are implicated in a wide variety of tumours including approximately 10% of paediatric ALL patients though the incidence is higher in TALL. The region has been the subject of much study but deletion of the potential tumour suppressor gene P16, or Cyclin-Dependent Kinase Inhibitor 2a was found to take place in 90% of newly diagnosed (cytogenetic deletions of 9p21) cases of Paediatric ALL by FISH. This study showed that deletion of P16 only, rather than both P16 and P15 (CDKN2B), was the critical step, as one case was found to be deleted for P16 but P15 was present. The deletion is usually homozygous (81% compared to 9% hemizygous) in cases of T-ALL, whilst homozygous and hemizygous deletions are roughly equal in B –ALL (23% vs. 20% for homozygous and hemizygous respectively). The gene inhibits the Cyclin Dependent Kinases CDK4 and CDK6, which are important in controlling the cell cycle from G1 to S phase so disruptions of this process are likely to result in the proliferation of mutated cells.

The P16 probe, labelled in red, covers a 101 kb region of 9p21, extending from 59 kb 3’ of P16 to the 5’ end of P15. The probe mix also contains a control probe for chromosome 9 (D9Z3, the heterochromatic block at 9q12).