Paraganglioma/pheochromocytoma
Below is a detailed description of the designated genes ( RET, SDHAF2, SDHB, SDHC, SDHD, VHL ). These genes are mainly involved in cell growth, metabolism, and tumor suppression , and play important roles especially influencing endocrine tumors and metabolism-related cancers.
1. RET (Rearranged during Transfection)
- Role : RET is a receptor tyrosine kinase that regulates cell proliferation, differentiation, and migration . This gene plays an important role in neural crest cell and thyroid development. Activation of the RET signaling pathway promotes cell proliferation.
- Associated diseases :
- Multiple endocrine neoplasia type 2 (MEN2) : Mutations in RET increase the risk of endocrine tumors, including medullary thyroid cancer (MTC) and pheochromocytoma.
- Thyroid cancer : RET gene abnormalities are one of the leading causes of thyroid cancer.
2. SDHAF2 (Succinate Dehydrogenase Complex Assembly Factor 2)
- ROLE : SDHAF2 is part of the succinate dehydrogenase complex (SDH, complex II) and participates in the assembly of this complex. SDH is involved in the mitochondrial electron transport chain and plays a key role in cellular energy production.
- Associated diseases :
- Adrenal medullary tumors (pheochromocytoma) and paragangliomas . Mutations in SDHAF2 increase the risk of these tumors, which are usually endocrine-related tumors.
3. SDHB (Succinate Dehydrogenase Complex Subunit B)
- ROLE : SDHB is part of the succinate dehydrogenase complex and is involved in the mitochondrial electron transport chain and the citric acid cycle . SDHB aids in energy production and maintains cellular redox balance.
- Associated diseases :
- Adrenal medullary tumors and paragangliomas . Mutations in SDHB increase the risk of these tumors.
- Familial tumor syndromes : SDHB mutations are associated with familial occurrence of these tumors.
4. SDHC (Succinate Dehydrogenase Complex Subunit C)
- Role : SDHC is also part of the succinate dehydrogenase complex and plays a key role in the mitochondrial electron transport chain. SDHC regulates energy production and redox reactions.
- Associated diseases :
- Adrenal medullary tumors and paragangliomas . Mutations in SDHC increase the risk of developing these tumors. These tumors primarily affect the endocrine and nervous systems.
5. SDHD (Succinate Dehydrogenase Complex Subunit D)
- Role : SDHD is part of the succinate dehydrogenase complex and cooperates with SDHB and SDHC to regulate redox reactions in the mitochondrial electron transport chain. SDHD plays a key role in cellular energy production.
- Associated diseases :
- Adrenal medullary tumors and paragangliomas . Mutations in SDHD increase the risk of developing these tumors, and they often occur in families.
6. VHL (Von Hippel-Lindau Tumor Suppressor)
- Role : VHL is a tumor suppressor gene involved in the oxygen sensing system and regulates the degradation of HIF (hypoxia inducible factor) under hypoxic conditions, thereby controlling angiogenesis and cell proliferation and suppressing tumor development.
- Associated diseases :
- Von Hippel-Lindau disease (VHL disease) : Mutations in VHL increase the risk of renal cell carcinoma , cerebral angiomas , pheochromocytomas , and retinal angiomas .
summary
These genes are mainly involved in the control of mitochondrial energy metabolism and cell proliferation , and are particularly associated with endocrine tumors such as adrenal medullary tumors, paragangliomas, and thyroid cancer. In particular, RET is associated with multiple endocrine neoplasia, and VHL is the causative gene for von Hippel-Lindau disease. Mutations in SDHB, SDHC, and SDHD , subunits of the SDH complex , cause defects in mitochondrial function and increase the risk of developing these tumors.