'Pituitary tumours' is an umbrella term for various tumours originating from different regions of the hypothalamic-pituitary system. The vast majority of pituitary tumours are pituitary adenomas, also recently referred to as pituitary neuroendocrine tumours (PitNET). The prevalence of clinically relevant pituitary adenomas is approximately 1 in 1000; other pituitary tumours such as craniopharyngioma and pituicytoma are comparatively very rare. This review addresses the molecular and genetic aspects of pituitary adenomas. We first discuss the germline genetic variants underlying familial pituitary tumours, which account for approximately 5% of all pituitary adenoma cases. This includes variants in established pituitary adenoma/hyperplasia predisposition genes (MEN1, PRKAR1A, AIP, CDKN1B, GPR101, SDHA, SDHB, SDHC, SDHD, SDHAF2) as well as emerging genetic associations. In addition, we discuss McCune-Albright syndrome which lies between the germline and somatic pituitary tumour genes as the causative GNAS mutations are postzygotic rather than being inherited, and the condition is associated with multiglandular features due to involvement of different cell lines rather than being limited to the pituitary. By contrast, somatic GNAS mutations contribute to sporadic acromegaly. USP8 is the only other gene where somatic driver mutations have been established in sporadic pituitary tumorigenesis. However, there are now known to be a variety of other somatic genetic and molecular changes underpinning sporadic pituitary adenomas which we will review, namely: copy number variation, molecular changes in signalling and hypoxia pathways, epithelial-mesenchymal transition, DNA repair, senescence, the immune microenvironment and epigenetics.
Keyphrases
- copy number
- growth hormone
- genome wide
- mitochondrial dna
- dna repair
- epithelial mesenchymal transition
- endothelial cells
- stem cells
- magnetic resonance
- dna methylation
- randomized controlled trial
- systematic review
- magnetic resonance imaging
- gene expression
- risk factors
- preterm infants
- early onset
- fatty acid
- single molecule
- amyotrophic lateral sclerosis
- signaling pathway
- contrast enhanced