Table 2.

Somatic genetic alterations of PitNET (Pituitary adenoma) and their clinicopathologic relevance

Gene(s)	Molecular pathology	PitNET (Pituitary Adenoma) type(s)	Clinicopathologic implications	Reference(s)
ATRX	Nonsense mutations, frameshift indels, and rarely intragenic deletions inactivate ATRX, promoting telomere instability and cells immortality	Corticotroph	Aggressive, recurrent, metastatic disease	[27]
GHR	Hetherozygous substitution of a single codon of GHR exon 4 affects the stability and/or processing of the GH-receptor	Sparsely granulated somatotroph	Therapeutic implications: response to GH-antagonists	[28–30]
GNAS	Missense mutations at Arg201 or Gln227 result in constitutive activity of Gs-alpha subunit (Gsα) which increases c-AMP levels	Densely granulated somatolactotroph	Florid acromegaly Small tumors Hypointensity on MRI T2 sequences Therapeutic implications: response to somatostatin analogues	[28, 31]
USP48	Missense mutations of USP48, including M415I/V substitution, result in enhanced proopiomelanocortin (POMC) gene’s promoter activity	Densely granulated USP8- wild-type corticotroph	Therapeutic implications: response to Pasireotide (due to high SSTR5 expression)	[32]
USP8	Missense mutations, primarily in exon 14, of the Ubiquitin Specific Peptidase gene determine ACTH degradation and increased deubiquitination of EGFR	Densely granulated corticotroph	Florid Cushing disease Small tumors Therapeutic implications: response to Pasireotide (due to high SSTR5 expression)	[33–37]