Current understanding of the role of DNA methylation in pituitary neuroendocrine tumors

Abstract

Pituitary neuroendocrine tumors (PitNETs) are unusual among neoplasms in that sporadic tumors are not typically associated with genetic mutations. Instead, epigenetics, a non-mutational process by which gene expression is modified via a variety of mechanisms, may be a driving factor in PitNET growth and behavior. DNA methylation is one of the most well-understood forms of epigenetic modification. Research on DNA methylation profiles of PitNETs has identified a large number of genes silenced or upregulated by DNA methylation, particularly when methylated at CpG islands of gene promoter regions. Global patterns of DNA methylation may provide valuable insight into the origins of pituitary adenoma subtypes, assist with PitNet diagnostics, and have been found to correspond to the current World Health Organization classification of PitNETs based on transcription factor lineage. Analysis of differentially methylated regions of individual genes may have prognostic value as well as guide research toward nonsurgical therapeutic strategies. Pituitary epigenetics and DNA methylation analysis are rapidly growing areas of interest with the potential to shape the future of pituitary tumor diagnostics and treatment.