Pituitary tumours: all silent on the epigenetics front

Abstract

Investigation of the epigenome of sporadic pituitary tumours is providing a more detailed understanding of aberrations that characterise this tumour type. Early studies, in this and other tumour types adopted candidate-gene approaches to characterise CpG island methylation as a mechanism responsible for or associated with gene silencing. However, more recently, investigators have adopted approaches that do not require a priori knowledge of the gene and transcript, as example differential display techniques, and also genome-wide, array-based approaches, to 'uncover' or 'unmask' silenced genes. Furthermore, through use of chromatin immunoprecipitation as a selective enrichment technique; we are now beginning to identify modifications that target the underlying histones themselves and that have roles in genesilencing events. Collectively, these studies provided convincing evidence that change to the tumour epigenome are not simply epiphenomena but have functional consequences in the context of pituitary tumour evolution. Our ability to perform these types of studies has been and is increasingly reliant upon technological advances in the genomics and epigenomics arena. In this context, other more recent advances and developing technologies, and, in particular, next generation or flow cell re-sequencing techniques offer exciting opportunities for our future studies of this tumour type.

Treatment of pituitary neoplasms with temozolomide

“…It has been demonstrated that, in pituitary tumors, promoter methylation is a frequent event. 55,56 Bello et al 57 reported that MGMT was methylated at significant rates in both functional and nonfunctional adenomas. This epigenetic alteration may disrupt the key cellular functions of MGMT and contribute to pituitary adenoma development.…”

Epidrug mediated re-expression of miRNA targeting the HMGA transcripts in pituitary cells

“…[2] In common with most other tumour types the genesis of pituitary tumours is consequent to the combined contribution of genetic and epigenetic aberration, targeting the genome and epigenome respectively. [3,4,2,5] The relative contributions of these aberrations, their order of appearance, and the way in which their effects are manifest are largely unknown, however, specific aberration, be they genetic or epigenetic, are either common or particular to an adenoma subtype(s). [6,5,7] Moreover, the demarcation between genetic and epigenetic aberrations are perhaps less precise than initial findings suggested.…”

β-Catenin stimulates pituitary stem cells to form aggressive tumors

“…Their studies provide a mechanism underlying a common, problematic intracranial neoplasm affecting children, and the animal model they developed accurately predicted markers in human craniopharyngiomas. This work represents an important step in understanding the etiology of pituitary adenomas and sets the stage for exploring the role of epigenetics and tumor suppressors in normal and abnormal pituitary development (27).…”

“…Gaston-Massuet et al clearly show that mutants do not express Pou1f1 or the target genes growth hormone and thyroid stimulating hormone at the appropriate time, and Pou1f1 expression is blocked in mutant pituispheres (3). Further studies will reveal the complete mechanism of Pou1f1 regulation, including the role of corepressors, epigenetic regulation, and microRNAs (25)(26)(27).…”