However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.
We present an adolescent male with an SDH-deficient GIST and SDHC germline mutation who developed bilateral renal cysts and neck cysts, not previously described in children with this mutation.
The genes for SDHA, SDHB, SDHC, and SDHD are located in the nuclear DNA, and mutations in these genes have initially been described in paragangliomas (PGL) and pheochromocytomas (PCC), which are relatively rare tumors derived from the autonomic nervous system and the adrenal medulla, respectively.
The genes for SDHA, SDHB, SDHC, and SDHD are located in the nuclear DNA, and mutations in these genes have initially been described in paragangliomas (PGL) and pheochromocytomas (PCC), which are relatively rare tumors derived from the autonomic nervous system and the adrenal medulla, respectively.
Additionally, attenuated SDH activity following SDHC knockdown promoted HCC-cell growth and metastasis both in vitro and in vivo via elevated reactive oxygen species levels and subsequent activation of nuclear factor-κB signaling.
Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma).
To our knowledge, this is the first case of a sporadic parasympathetic PGL that carries silencing of SDHC, fulfilling the two-hit Knudson's model for tumorigenesis.
Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma).
Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma).
Other tumors (outside CT and CSS) that have SDH deficiency are associated with increased methylation of the entire genome, but only in CT there is site-specific methylation of the SDHC gene.
Thirty per cent are associated with SDHA germline mutation and 50% are associated with SDHC epimutation (post-zygotic promoter hypermethylation) - the hallmark of the syndromic but non-hereditary Carney triad (SDH- deficient GIST, SDH-deficient paraganglioma and pulmonary chondroma).
To our knowledge, this is the first case of a sporadic parasympathetic PGL that carries silencing of SDHC, fulfilling the two-hit Knudson's model for tumorigenesis.
Other tumors (outside CT and CSS) that have SDH deficiency are associated with increased methylation of the entire genome, but only in CT there is site-specific methylation of the SDHC gene.
An alternate mechanism leading to GIST oncogenesis is deficiency in the succinate dehydrogenase (SDH) enzyme complex resulting from genetic or epigenetic inactivation of one of the four SDH subunit genes (SDHA, SDHB, SDHC, SDHD, collectively referred to as SDHX).
We present a case of adolescent girl who presented with isolated Raynaud's phenomenon as only manifestation of metastasis of PGL 3 years after undergoing surgical excision of normetanephrine secreting abdominal PGL.
A total of 121 consecutive, unrelated, index PCC/PGL patients underwent genetic testing for five PCC/PGL susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) and were evaluated for clinical diagnosis of neurofibromatosis type1 (NF1).