P16 Deletion LPH009 - Detail

Deletions of chromosome 9p21 are implicated in a wide variety of tumours including approximately 10% of paediatric ALL patients¹ though the incidence is higher in T-ALL². The region has been the subject of much study but deletion of the potential tumour suppressor gene P16 or Cyclin-Dependent Kinase Inhibitor 2a (CDKN2A) was found to take place in 90% of newly diagnosed cases of paediatric ALL showing cytogenetic deletions of 9p21by FISH³. 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 product 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.

Reference:/Bibliographie/Literatur/Bibliografia

1. Heerema et al., 1999. Leukemia 13(5): 679-686
2. Secker-Walker et al., 1997. Br J Haematol. 96(3): 601-10.
3. Okuda et al., 1995. Blood. 85(9):2321-30.