Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832526 (PCC)
 5,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pheochromocytomas and paragangliomas (PCC/PGL) are the solid tumour type most commonly associated with an inherited susceptibility syndrome. However, very little is known about the somatic genetic changes leading to tumorigenesis or malignant transformation. Here we perform whole-exome sequencing on a discovery set of 21 PCC/PGL and identify somatic ATRX mutations in two SDHB-associated tumours. Targeted sequencing of a separate validation set of 103 PCC/PGL identifies somatic ATRX mutations in 12.6% of PCC/PGL. PCC/PGL with somatic ATRX mutations are associated with alternative lengthening of telomeres and clinically aggressive behaviour. This finding suggests that loss of ATRX, an SWI/SNF chromatin remodelling protein, is important in the development of clinically aggressive PCC/PGL.
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PMID:Whole-exome sequencing identifies somatic ATRX mutations in pheochromocytomas and paragangliomas. 2560 29

Paragangliomas are rare neuroendocrine tumors which originate from embryonic neural crest cells. These tumors may arise from parasympathetic or sympathetic paraganglia, may secrete catecholamines, and can occur in varied anatomic locations, with some locations being less common than others. Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas and pheochromocytomas and have been associated with germline heterozygous mutations in MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, or TMEM127. Herein, we report a case of a middle-aged male who was diagnosed with an intrarenal/renal pelvis paraganglioma after presenting in hypertensive crisis with palpitations, headache, and diaphoresis. He was later found to have extensive metastatic disease, as well as genetic testing that showed biallelic inactivation of SDHB and a co-occurring somatic ATRX mutation. Respectively, these germline and somatic mutations have been associated with increased risk of metastatic spread and clinical aggressiveness. Despite multiple surgical resections and various treatment modalities, the patient eventually elected for palliative care measures and died of disease. Together, the findings seen in this patient are unique and serve as an appropriate catalyst for discussing the unusual locations, interesting genetic profiles, and metastatic risk factors that may be associated with paragangliomas.
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PMID:Malignant Intrarenal/Renal Pelvis Paraganglioma with Co-Occurring SDHB and ATRX Mutations. 3170 39