Table 4.
Human syndromes predisposing for PitNETs.
| syndromes predisposing to PitNETs | ||||||
|---|---|---|---|---|---|---|
| disease | cases per million | inheritance | phenotype (tumor hormone production) |
frequently mutated genes | (potential) HH signaling … | |
| Neurofibromatosis syndrome type 1 | 300 -400 | autosomal dominant | optic pathway gliomas, high GH levels, rarely PitNETs, empty sella, hypopituitarism | NF1 (reviewed in (220)) | … is involved in tumorigenesis of NF1 tumors (221) | |
| Lynch syndrome | 330 | autosomal dominant | PitNETs (ACTH) |
EPCAM, MLH1, MLH3, MSH2, MSH6, PMS2, TGFBR2 (222, 223) | … inhibition by TGFBR2 in cancer (224) | |
| MEN | type 1 | 33 - 100 | autosomal dominant | MEN1 (193) | MEN1 (193) | … activation due to activating Men1/MEN1 mutation (210, 225) |
| type 2 | 28 | autosomal dominant | RET (193) | RET (193) | … activation due to activating RET mutations (226) | |
| von Hippel–Lindau syndrome | 27 | autosomal dominant | pituitary stalk hemangioblastomas | VHL (227) | … activation due to VHL mutation (228) | |
| hypothalamic hamartoma | est. 1 - 20 | sporadic/5% Pallister Hall syndrome | clusters of small neurons intermixed with glia and large neurons, GHD, TSHD, posterior pituitary dysfunction | GLI3, OFD1, SOX2 (161, 229, 230) | … inactivation due to SOX2, GLI3 mutations (161, 230) … mutations enriched in hamartomas (161, 230) |
|
| McCune-Albright | 1 - 10 | postzygotic (non-germline) | 14% pituitary hyperplasia, 6% PitNETs (GH, PRL), |
GNAS (postzygotic, activating) (231) | … activation due to GNAS null mutations (198–200) | |
| Carney complex | (160 cases) | autosomal dominant | pituitary hyperplasia, 20% PitNETs (GH/PRL) |
PRKAR1A
,
PRKACB
( 232) |
… inhibition by PKA signaling (209) | |
| DICER1 syndrome | (1,000 cases) | potential autosomal recessive | pituitary blastoma PitNETs (ACTH) |
DICER1 (233, 234) | … dependent pathologies are influenced by Dicer1 (194) | |
est., estimated; MEN, multiple endocrine neoplasia.
Not listed are MEN syndrome type 4 and 5, MEN-like syndrome, Familial isolated pituitary adenoma, Familial infantile gigantism and Succinate dehydrogenase deficiency. Genes associated with HH signaling are highlighted in bold.