Table 3.
HH signaling and PitNETs.
| pituitary neuroendocrine tumors (PitNETs)/adenomas | ||||||
|---|---|---|---|---|---|---|
| disease | subtype | cases per million | origin | phenotype/ tumor hormone production |
frequently mutated genes (94) | potential HH signaling … |
| TPIT+ PitNETs | corticotroph | ~150 | supposedly hormone-secreting cells | ACTH | AIP, ATRX, BRAF1, DICER1 , FGFR2 , GNAS , MLH1, NR3C1 , PABPC1, SH2, TP53, TSP-1 , USP8 , USP48 (94, 100, 193) | … activation in ACTH PitNETs (11) … dependent pathologies are non-additively influenced by Dicer1 (194) … activation by FGFR2 signaling (195–197) … activation due to GNAS null mutations (198–200) … inhibition by NR3C1 signaling (201) … activation by TSP-1 null mutation (202) … activation by USP48-mediated GLI1 stabilization (203, 204) … activation by USP8 (205) |
| PIT1+ PitNETs | somatotroph | >150 | GH and/or αGSU | AIP, GNAS , GRB101, PRKAR1A , MEN1 , MAX, SDHD (94, 100, 193, 206–208) | … activation in GH PitNETs (11) … activation due to GNAS null mutations (198–200) … inactivation by PKA signaling (209) … activation due to MEN1 mutation (210) |
|
| lactotroph | n. a. | PRL | AIP, HMGA2, PRKAR1A , MEN1 , KIF5A, MAX, SDH, SF3B1 (94, 206–208) | … activation in PRL PitNETs (11) … inactivation by PKA signaling (209) … activation due to MEN1 mutation (210) |
||
| thyrotroph | TSH | ASTN2, CWH43, R3HDM2, SMOX, SYTL3, THRb , ZSCAN23 (211) | … regulation byTHR (212) | |||
| NFPA | – | n. a. | none | CDKN2A, ENC1, FAM90A1, ING2, MEG3, MLH3, MSH5, MSH6, PI3K (213) | … activation by MEG3 inhibition (214) | |
NFPA, non-functioning pituitary adenoma; PitNET, pituitary neuroendocrine tumor.
Not listed are mammasomatotroph, mature plurihormonal, immature PIT-1 lineage, acidophil stem cell, gonadotroph and undefined PitNETs. Genes associated with HH signaling are highlighted in bold.