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Metastatic sympathetic paraganglioma in a patient with loss of the SDHC gene

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Abstract

Mutation of the genes encoding the succinate dehydrogenase (SDH) subunits A, B, C, or D, or the SDHAF2 protein, cause the SDHx-hereditary paraganglioma syndromes. Hereditary susceptibility to metastatic sympathetic pheochromocytomas and paragangliomas is most commonly due to germline mutations in the SDHB gene. Individuals with SDHD mutations occasionally present with metastatic disease, while conversely malignant paragangliomas are rarely observed in SDHC carriers. A 43 year-old woman presented with an abdominal paraganglioma metastatic to the skeleton and multiple lymph nodes. The tumor produced excessive amounts of noradrenaline causing hypertension and symptoms of catecholamine excess. The patient underwent surgical resection of the primary tumor and lymph node metastases. Loss of SDHB protein expression in the primary tumor was demonstrated by immunohistochemistry. Germline sequencing and deletion testing revealed a large allelic deletion of exons 1–6 in SDHC, and no mutations or deletions were detected in SDHB or SDHD. The patient’s mother died because of kidney cancer. Hereditary pheochromocytomas and paragangliomas may be associated with a deletion of the SDHC gene. These patients may present with malignant sympathetic paragangliomas.

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Authors and Affiliations

  1. Myriad Genetic Laboratories, Salt Lake City, UT, USA

    Thereasa Rich

  2. Clinical Cancer Genetics Department, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Michelle Jackson

  3. Department of Endocrinology, Hospital San Vicente Fundacion, Universidad de Antioquia, Medellín, Colombia

    Alejandro Roman-Gonzalez

  4. Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Komal Shah

  5. Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street Unit 1461, Houston, TX, 77030, USA

    Alejandro Roman-Gonzalez, Gilbert J. Cote & Camilo Jimenez

Authors
  1. Thereasa Rich
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  2. Michelle Jackson
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  3. Alejandro Roman-Gonzalez
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  4. Komal Shah
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  5. Gilbert J. Cote
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  6. Camilo Jimenez
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Correspondence to Camilo Jimenez.

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Rich, T., Jackson, M., Roman-Gonzalez, A. et al. Metastatic sympathetic paraganglioma in a patient with loss of the SDHC gene. Familial Cancer 14, 615–619 (2015). https://doi.org/10.1007/s10689-015-9821-0

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  • DOI: https://doi.org/10.1007/s10689-015-9821-0

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