Tumour suppressor genes in pituitary tumour formation

Studies of the molecular changes that characterize pituitary tumours have gone 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 tumours, while losses on 9p occur early in pituitary tumorigenesis. Studies of known 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 associated with methylation of this geneʹs CpG island and is an early change in non-functional tumours. The enforced expression ofp16/CDKN2A in the AtT20 cell line has shown that it is responsible for G1arrest, mimicking its in vivo role. Methylation may provide a unifying mechanism preceding and predisposing towards allelic loss, and in other cases leading to reduced tumour suppressor gene expression. Pharmacological interventions designed to induce the re-expression of genes silenced through this mechanism offer considerable therapeutic potential.