High Frequency ofSDHBGermline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing
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Open Access
- 1 November 2006
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 91 (11) , 4505-4509
- https://doi.org/10.1210/jc.2006-0423
Abstract
Context: Adrenal and extraadrenal paragangliomas are tumors of chromaffin cells that are usually benign but that may also develop into malignant disease. Mutations of the gene for succinate dehydrogenase subunit B (SDHB) are associated with a high risk of malignancy, but establishing the precise contribution requires relatively large numbers of patients with well-defined malignancy. Objective: We assessed the prevalence of SDHB mutations in a series of patients with malignant paraganglioma. Design:SDHB mutation testing was carried out in 44 consecutive patients with malignant paraganglioma. Clinical characteristics of patients with malignant disease due to SDHB mutations were compared with those without mutations. Results: Pathogenic SDHB mutations were found in 13 of the 44 patients (30%). Close to one third of patients had metastases originating from an adrenal primary tumor, compared with a little over two thirds from an extraadrenal tumor. Among the latter patients, the frequency of SDHB mutations was 48%. Conclusion: This study establishes that missense, nonsense, frameshift, and splice site mutations of the SDHB gene are associated with about half of all malignancies originating from extraadrenal paragangliomas. The high frequency of SDHB germline mutations among patients with malignant disease, particularly when originating from an extraadrenal paraganglioma, may justify a high priority for SDHB germline mutation testing in these patients.Keywords
This publication has 22 references indexed in Scilit:
- Clinical Presentation and Penetrance of Pheochromocytoma/Paraganglioma SyndromesJournal of Clinical Endocrinology & Metabolism, 2006
- Genetic Testing in Pheochromocytoma or Functional ParagangliomaJournal of Clinical Oncology, 2005
- PhaeochromocytomaThe Lancet, 2005
- Distinct Clinical Features of Paraganglioma Syndromes Associated With SDHB and SDHD Gene MutationsJAMA, 2004
- A Novel Succinate Dehydrogenase Subunit B Gene Mutation, H132P, Causes Familial Malignant Sympathetic Extraadrenal ParagangliomasJournal of Clinical Endocrinology & Metabolism, 2004
- Familial Malignant Catecholamine-Secreting Paraganglioma with Prolonged Survival Associated with Mutation in the Succinate Dehydrogenase B GeneJournal of Clinical Endocrinology & Metabolism, 2002
- Germ-Line Mutations in Nonsyndromic PheochromocytomaNew England Journal of Medicine, 2002
- Gene Mutations in the Succinate Dehydrogenase Subunit SDHB Cause Susceptibility to Familial Pheochromocytoma and to Familial ParagangliomaAmerican Journal of Human Genetics, 2001
- Clinical Differences between Benign and Malignant Pheochromocytomas.Endocrine Journal, 2001
- Mutations in SDHD , a Mitochondrial Complex II Gene, in Hereditary ParagangliomaScience, 2000