Epigenetics of pituitary tumours: an update

To review recent advances in our knowledge and understanding of aberrations that target the epigenome in sporadic pituitary adenomas.

A more complete understanding of the pituitary epigenome has been facilitated by advances in technologies for exploring the tumour-associated epigenomic landscape, and has revealed aberration to the principle targets of these changes, namely, methylation of CpG dinucleotides, modification of histone tails and the expression of target-specific miRNA. Genome-wide investigations, of sporadic pituitary adenoma, have identified novel methylated genes that in some cases are subtype-specific. Recent studies have also shown that silenced genes may be reactivated through epidrug challenges. Moreover, in experimental settings, wherein enforced expression of specific miRNA has been employed, these have been shown to inhibit pituitary cell proliferation in vitro and in vivo.

Candidate gene and genome-wide studies reveal frequent epigenetic changes in pituitary adenomas. Aberrations, concurrent with their impact on functional end-points, may display subtype specificity, whereas others appear to be independent of adenoma subtype. Changes to the epigenomic landscape, and apparent as CpG island methylation and/or as histone tail modifications, show sensitivity to epidrug-induced re-expression that concomitantly impacts on cell proliferation. Similarly, enforced expression of silenced miRNA in model systems is also associated with similar end-points. Collectively, emerging data show that these types of manipulation, alone or in combination with a more conventional therapeutic option, offer new avenues for the medical management of these tumours.