Syndrome/name | Gene | Typical tumor location and other associations |
Pseudo-hypoxic – Cluster 1* | ||
SDHD mutation (familial paraganglioma type 1)¶ | SDHD | Primarily skull base and neck; occasionally adrenal medulla, mediastinum, abdomen, pelvis; GIST; possible pituitary adenoma |
SDHAF2 mutation (familial paraganglioma type 2)¶ | SDHAF2 | Primarily skull base and neck; occasionally abdomen and pelvis |
SDHC mutation (familial paraganglioma type 3) | SDHC | Primarily skull base and neck; occasionally abdomen and pelvis; GIST; possible pituitary adenoma |
SDHB mutation (familial paraganglioma type 4) | SDHB | Abdomen, pelvis and mediastinum; rarely adrenal medulla, skull base, and neck; GIST; possible pituitary adenoma |
SDHA mutation | SDHA | Primarily skull base and neck; occasionally abdomen and pelvis; GIST; possible pituitary adenoma |
VHL disease | VHL | Adrenal medulla, frequently bilateral; occasionally paraganglioma that may be localized from skull base to pelvis |
Hereditary leiomyomatosis and renal cell carcinoma (Reed syndrome) – Fumarate hydratase mutation | FH | Multifocal and metastatic; associated with hereditary leiomyomatosis, uterine fibroids, and renal cell cancer |
Hypoxia inducible factor 2-alpha | EPAS1 (HIF2A) | Paraganglioma, polycythemia, and rarely somastostatinoma |
Familial erythrocytosis associated with mutation in prolyl hydroxylase isoform 1 (PDH1) | EGLN2 | Polycythemia associated with pheochromocytoma and paraganglioma |
Familial erythrocytosis associated with mutation in prolyl hydroxylase isoform 2 (PDH2) | EGLN1 | Polycythemia associated with pheochromocytoma and paraganglioma |
Kinesin Family Member 1B gene | KIF1B | Neuroblastoma |
DNA methyltransferase 3-alpha gene | DNMT3A | Skull base and neck paraganglioma |
Dihydrolipoamide S-succinyltransferase gene | DLST | PGL7 tumor predisposition syndrome; pheochromocytoma and thoraco-abdominal paragangliomas |
Succinate-CoA ligase GDP-forming subunit beta gene | SUCLG2 | Paraganglioma |
Kinase signaling pathway – Cluster 2Δ | ||
MEN2A and MEN2B | RET | Adrenal medulla, frequently bilateral |
Neurofibromatosis type 1 | NF1 | Adrenal or peri-adrenal |
MAX¶ | MAX | Adrenal medulla |
Familial pheochromocytoma | TMEM127 | Adrenal medulla; possible renal cell carcinoma |
HRAS proto-oncogene, GTPase | HRAS | |
Wnt signaling pathway – Cluster 3◊ | ||
Cold shock domain E1 | CSDE1 | Sporadic, aggressive disease with frequent recurrence and metastases |
UBTF (Upstream Binding Transcription Factor) fusion with MAML3 (mastermind like transcriptional coactivator 3) | UBTF::MAML3 fusion | Sporadic, aggressive disease with frequent recurrence and metastases |
GIST: gastrointestinal stromal tumor; MEN2: multiple endocrine neoplasia type 2; SDH: succinate dehydrogenase; VHL: von Hippel-Lindau.
* Cluster 1 tumors are mostly extra-adrenal paragangliomas (except in VHL, where most tumors are localized to the adrenal), and nearly all have a noradrenergic biochemical phenotype.
¶ Associated with maternal imprinting.
Δ Cluster 2 tumors are usually adrenal pheochromocytomas with an adrenergic biochemical phenotype.
◊ Cluster 3 tumors can have a noradrenergic or adrenergic biochemical phenotype.Do you want to add Medilib to your home screen?