High Frequency of<i>SDHB</i>Germline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing

Brouwers, Frederieke M.; Eisenhofer, Graeme; Tao, Jessica; Kant, Jeffrey A.; Adams, Karen T.; Linehan, W. Marston; Pacák, Karel

doi:10.1210/jc.2006-0423

Cited by 291 publications

(219 citation statements)

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“…Genetic evaluation can be of assistance in this situation, where one can predict a higher tendency towards the development of malignant disease with metastases in patients harbouring certain mutations (e.g. mutations of SDHB lead to metastatic disease in 40% or more of affected patients, or less commonly seen MAX and FH mutations) (4,5). In fact, germline genetic forms of phaeochromocytoma are often multiple, extra-adrenal and recurrent; consequently, regular surveillance and strict follow-up is recommended for better prognosis of such patients.…”

Section: Clinical Implications Of Genetic Testingmentioning

confidence: 99%

“…Typically, they originate from extra-adrenal locations in the abdomen, thorax and the pelvis and are usually solitary tumours with a significantly high malignant potential (30%) (4,38). Therefore, all patients with metastatic phaeochromocytoma or paragangliomas should undergo SDHB mutation testing at the very least.…”

Section: Sdhb Mutationmentioning

confidence: 99%

“…In addition, bilateral phaeochromocytomas are mostly found with these same mutations (11,12,14,21,26,42,45,53). On the other hand, SDH mutations cause intra-adrenal tumours less commonly; 25% of SDHB-related tumours are phaeochromocytomas while the frequency of intraadrenal tumours in SDHD, SDHA and SDHC are even lower (4,7,36,37,41,53). Most of the extra-adrenal tumours are due to mutations in SDH genes (4,7,36,37,40,53).…”

Section: Location Of the Tumourmentioning

confidence: 99%

“…On the other hand, SDH mutations cause intra-adrenal tumours less commonly; 25% of SDHB-related tumours are phaeochromocytomas while the frequency of intraadrenal tumours in SDHD, SDHA and SDHC are even lower (4,7,36,37,41,53). Most of the extra-adrenal tumours are due to mutations in SDH genes (4,7,36,37,40,53). Apart from which, extra-adrenal tumours were also found in rare EGLN1 mutation (47).…”

Section: Location Of the Tumourmentioning

confidence: 99%

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The clinical genetics of phaeochromocytoma and paraganglioma

Gunawardane

Grossman

2017

Arch. Endocrinol. Metab.

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Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500

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Section: Clinical Implications Of Genetic Testingmentioning

confidence: 99%

Section: Sdhb Mutationmentioning

confidence: 99%

Section: Location Of the Tumourmentioning

confidence: 99%

Section: Location Of the Tumourmentioning

confidence: 99%

See 2 more Smart Citations

The clinical genetics of phaeochromocytoma and paraganglioma

Gunawardane

Grossman

2017

Arch. Endocrinol. Metab.

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“…Indeed, it has been found that malignant pheochromocytoma/paraganglioma is associated with 38 to 83% of patients with SDHB germline mutations, indicating a much higher rate of malignancy compared with other mutations or sporadic adrenal pheochromocytoma where the rate is <10%. Conversely, among all patients with malignant pheochromocytoma/ paraganglioma the frequency of SDHB mutations is reported to be around one third, suggesting that SDHB mutations in these malignant tumors may not be as rare as expected [9]. Previously, we identified a novel heterozygous G to A point mutation at the first base of intron 3 of the SDHB gene (IVS3+1G>A) in a malignant abdominal paraganglioma from a Japanese patient.…”

mentioning

confidence: 91%

R46Q Mutation in the Succinate Dehydrogenase B Gene (SDHB) in a Japanese Family with both Abdominal and Thoracic Paraganglioma Following Metastasis

et al. 2008

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Abstract. Recently, nuclear genes encoding two mitochondrial complex II subunit proteins, SDHD and SDHB, have been found to be associated with the development of familial pheochromocytomas and paragangliomas (hereditary pheochromocytoma/paraganglioma syndrome: HPPS). Growing evidence suggests that a mutation of SDHB is highly associated with abdominal (or thoracic) paraganglioma and the following distant metastasis (malignant paraganglioma). Previously, we identified a novel heterozygous G to A point mutation at the first base of intron 3 of the SDHB gene (IVS3+1G>A) in a malignant abdominal paraganglioma from a Japanese patient. In the present study, we report another case of SDHB mutation (R46Q) in a Japanese patient with both abdominal and thoracic paraganglioma following malignant metastasis. In addition, we identified an asymptomatic carrier of SDHB mutation in this family. Our report highlights the pathogenic role of the SDHB mutation (R46Q) in malignant paraganglioma. We also discuss the desired protocol that should be adopted to follow up an asymptomatic carrier of this mutation.

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Mitochondrial disorders of the OXPHOS system

2020

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Mitochondrial disorders are amongst the most frequent inborn errors of metabolism, their primary cause being the dysfunction of the oxidative phosphorylation system (OXPHOS). OXPHOS is composed of the electron transport chain (ETC), formed by four multimeric enzymes and two mobile electron carriers, plus an ATP synthase (also called complex V). The ETC performs the redox reactions involved in cellular respiration while generating the proton motive force used by complex V to synthesize ATP. OXPHOS biogenesis involves multiple steps, starting from the expression of genes encoded in physically separated genomes, namely the mitochondrial and nuclear DNA, to the coordinated assembly of components and cofactors building each individual complex and eventually the supercomplexes. The genetic cause underlying around half of the diagnosed mitochondrial disease cases is currently known. Many of these cases result from pathogenic variants in genes encoding structural subunits or additional factors directly involved in the assembly of the ETC complexes. Here we review the historical and most recent findings concerning the clinical phenotypes and the molecular pathological mechanisms underlying this particular group of disorders.

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High Frequency ofSDHBGermline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing

Cited by 291 publications

References 20 publications

The clinical genetics of phaeochromocytoma and paraganglioma

The clinical genetics of phaeochromocytoma and paraganglioma

R46Q Mutation in the Succinate Dehydrogenase B Gene (SDHB) in a Japanese Family with both Abdominal and Thoracic Paraganglioma Following Metastasis

Mitochondrial disorders of the OXPHOS system

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