Table 3.

Novel recurrently mutated somatic variants identified through whole exome sequencing studies.

Gene Associated with Variant, Symbol	Gene Name	Hormone Subtype	Mechanism of Tumorigenesis	References
NR3C1	Nuclear receptor subfamily 3 group C member 1	ACTH-PT	Glucocorticoid receptor. If mutated, this receptor may become insensitive to feedback from cortisol leading to ACTH over-production (171).	(142, 154, 161, 172)
MEN1	Menin 1	Plurihormonal (GH/PRL)	Inactivating mutations underlie multiple endocrine neoplasia type 1, an autosomal dominant syndrome with pituitary tumors as part of the phenotype.	(118, 142)
KIF5A	Kinesin heavy chain isoform 5A	PRL, GT	Modulates cell proliferation. Somatic mutations also found in prostate cancer (173).	(142)
GRB10	Growth factor receptor bound protein 10	GH-PT	Suppresses signals from activated receptors tyrosine kinases, including insulin-like growth factor type 1 receptors. Inactivating mutations may allow increased signaling facilitating somatotroph tumorigenesis.	(142)
BRAF	BRAF proto-oncogene, serine/threonine kinase	ACTH-PT	Elevated kinase activity with activation of MAPK pathway and transactivation of POMC, which is the precursor of ACTH. Well-established oncogenic roles in melanoma and multiple carcinomas.	(160, 161)
USP48	Ubiquitin specific peptidase 48	ACTH-PT	USP48 has been suggested to increase transcriptional activation of POMC through the NF-κB pathway, increase response to CRH and possibly involve the hedgehog pathway.	(160, 161)
PABPC1	poly (A) binding protein cytoplasmic 1	ACTH-PT	Binds the poly (A) tail of mRNA and is involved in regulatory processes such as pre-mRNA splicing and regulation of nonsense-mediated decay.	(120)
TP53	Cellular tumor antigen p53	ACTH-PT	Well-established tumor suppressor with role in cell cycle arrest, DNA repair and apoptosis induction.	(132)
SF3B1	Splicing factor 3b subunit 1	PRL	–	(141)