Tumour suppressor genes in pituitary tumour formation

Studies of the molecular changes that characterize pituitary tumours have g one some way towards increasing our understanding of the events responsible for their initiation and progression. Allelic deletions on chromosomes 10, 11 and 13 are significantly associated with invasive and metastatic rumour s, while losses on 9p occur early in pituitary tumorigenesis. Studies of kn own tumour suppressor genes within these regions of loss suggest a limited role, if any, in pituitary tumours. However, a loss of pRB is evident in a proportion of somatotrophinomas. Loss of p16 protein expression is associat ed with methylation of this gene's CpG island and is an early change in non -functional tumours. The enforced expression of p16/CDKN2A in the AtT20 cel l line has shown that it is responsible for G(1) arrest, mimicking its in v ivo role. Methylation may provide a unifying mechanism preceding and predis posing towards allelic loss, and in other cases leading to reduced tumour s uppressor gene expression. Pharmacological interventions designed to induce the re-expression of genes silenced through this mechanism offer considera ble therapeutic potential.