Disease relevance of Paraganglioma

• Our observations suggest that germline SDHB mutations can predispose to early-onset kidney cancers in addition to paragangliomas and carry implications for medical surveillance [1].
• Leiomyomas predominantly express VPAC2 receptors, whereas paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors [2].
• Surgical removal of the functioning paraganglioma and correction of the renal artery stenosis restored the postoperative plasma catecholamine, renin, and blood pressure to normal [3].
• Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas [4].
• BACKGROUND: Somatostatin receptors have been found on a variety of neuroendocrine tumours, such as carcinoids and paragangliomas, as well as on most pancreatic endocrine and breast tumours [5].

High impact information on Paraganglioma

• Mutations in SDHC cause autosomal dominant paraganglioma, type 3 [6].
• Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma [7].
• Carboplatin chemotherapy for malignant paraganglioma [8].
• In paraganglioma cells, two forms of SDHA (type I, II) were found which might preclude significant succinate accumulation in the case of a mutation in either form [9].
• A number of mutations in human SDH genes are responsible for the development of paragangliomas, cancers of the head and neck region [10].

Chemical compound and disease context of Paraganglioma

• Hereditary paraganglioma syndrome has recently been shown to be caused by germline heterozygous mutations in three (SDHB, SDHC, and SDHD) of the four genes that encode mitochondrial succinate dehydrogenase [1].
• In patients identified with catecholamine-secreting paragangliomas, the sensitivities achieved by measurements in the 24-h urine collection were 74% for total metanephrines, 84% for norepinephrine, 18% for dopamine, and 14% for epinephrine [11].
• Biochemical and clinical manifestations of dopamine-producing paragangliomas: utility of plasma methoxytyramine [12].
• Octreotide scintigraphy for the detection of paragangliomas [13].
• Localization and treatment of familial malignant nonfunctional paraganglioma with iodine-131 MIBG: report of two cases [14].

Biological context of Paraganglioma

• Founder effect at PGL1 in hereditary head and neck paraganglioma families from the Netherlands [15].
• Germline mutations in succinate dehydrogenase subunits B, C and D (SDHB, SDHC and SDHD), genes encoding subunits of mitochondrial complex II, cause hereditary paragangliomas and phaeochromocytomas [16].
• Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families [16].
• SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology [17].
• In order to characterize phenotypic effects of these mutations, the present study investigated the immunohistochemical expression of the catalytic subunits of complex II (flavoprotein and iron protein), SDH enzyme activity, and mitochondrial morphology in a series of 22 head and neck paragangliomas [17].

Anatomical context of Paraganglioma

• Germ-line mutations in the genes encoding succinate dehydrogenase complex subunits B (SDHB) and D (SDHD) have been reported in familial paragangliomas and apparently sporadic phaeochromocytomas (ASP), but the genotype-phenotype relationships of these mutations are unknown [18].
• Insulin-like growth factor (IGF)-II immunoreactivity was demonstrated in 14 adrenal glands, six retroperitoneal paraganglia, 18 phaeochromocytomas, and six extra-adrenal abdominal paragangliomas through the use of a monoclonal antibody against rat IGF-II which cross-reacts with human IGF-II [19].
• Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss [20].
• Skull base tumors: gadodiamide injection--enhanced MR imaging--drop-out effect in the early enhancement pattern of paragangliomas versus different tumors [21].
• Pancreatic somatostatin-secreting gangliocytic paraganglioma with lymph node metastases [22].

Gene context of Paraganglioma

• Germline SDHD mutations were originally described in hereditary paraganglioma, a dominantly inherited disorder characterized by vascular tumors in the head and the neck, most frequently at the carotid bifurcation [23].
• In addition, germline SDHD and SDHB mutations may cause phaeochromocytoma susceptibility with or without associated head and neck paragangliomas [24].
• E was found in a few neuroendocrine tissues outside of the adrenal, including cardiac paragangliomas, and the enzyme PNMT was localized in some of these neoplasms [25].
• Since 2000 the genes for succinatedehydrogenase subunits SDHB, SDHC, and SDHD have been identified for paraganglioma syndromes type 4, type 3, and type 1 respectively [26].
• Here we introduce all reported paraganglioma and pheochromocytoma related sequence variations in these genes, in addition to all reported mutations of SDHA [27].
• SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation [28].

Analytical, diagnostic and therapeutic context of Paraganglioma

• Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot [29]?
• In this study, we report the results of 111In-octreotide scintigraphy in 34 patients referred because of known paragangliomas or in whom a paraganglioma was suspected and compared the results of octreotide scintigraphy with the outcomes of other imaging techniques used in the diagnosis or follow-up of these patients [13].
• In situ hybridization confirmed that, as in other sites, liver paraganglioma can express IGF-II gene [30].
• Paraffin-embedded sections of 99 human adrenal and extraadrenal paragangliomas were analyzed by the indirect immunoperoxidase technique for the presence of neuron-specific enolase (NSE) and 10 neuropeptides [31].
• Routine staining showed that it had structural similarities to an ependymoma, but immunohistochemistry with antisera to synaptophysin, NSE, chromogranin-A and PGP 9.5 proved it to be a neuroendocrine tumor, i.e. a paraganglioma [32].

References