High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: Implications for genetic testing

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.31). 12/2006; 91(11):4505-9. DOI: 10.1210/jc.2006-0423
Source: PubMed

ABSTRACT 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.
We assessed the prevalence of SDHB mutations in a series of patients with malignant paraganglioma.
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.
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%.
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.

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