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Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series
Journal article   Open access   Peer reviewed

Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series

Tobias Else, Antonio Marcondes Lerario, Jessica Everett, Lori Haymon, Deborah Wham, Michael Mullane, Tremika LeShan Wilson, Irene Rainville, Huma Rana, Andrew J. Worth, …
European journal of endocrinology, v 177(5), pp 439-444
01 Nov 2017
DOI: https://doi.org/10.1530/EJE-17-0358
PMID: 28819017
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1530/eje-17-0358View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1530/EJE-17-0358View
Published, Version of Record (VoR) Open

Abstract

Endocrinology & Metabolism Life Sciences & Biomedicine Science & Technology
Objective: Germline loss-of-function mutations in succinate dehydrogenase (SDHx) genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor SDHx mutations. Patients and results: We report four unrelated patients with ACC and SDHx mutations. All cases presented with Cushing syndrome and large adrenal masses that were confirmed to be ACC on pathology. All four ACC specimens were found to have truncating mutations in either SDHC or SDHA, while cases 1, 2 and 3 also had the mutations confirmed in the germline: Case 1: SDHC c.397C > T, pR133X; Case 2: SDHC c.43C > T, p.R15X; Case 3: SDHA c.91C > T, p.R31X; Case 4: SDHA c.1258C > T, p.Q420X. Notably, Case 1 had a father and daughter who both harbored the same SDHC germline mutation, and the father had a paraganglioma and renal cell carcinoma. A combination of next generation sequencing, and/or immunohistochemistry, and/or mass spectroscopy was used to determine whether there was loss of heterozygosity and/or loss of SDH protein expression or function within the ACC. Potential evidence of loss of heterozygosity was observed only in Case 2. Conclusions: We observed truncating mutations in SDHA or SDHC in the ACC and/or germline of four unrelated patients. Given how statistically improbable the concurrence of ACC and pathogenic germline SDHx mutations is expected to be, these observations raise the question whether ACC may be a rare manifestation of SDHx mutation syndromes. Further studies are needed to investigate the possible role of SDH deficiency in ACC pathogenesis.

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21 citations in Web of Science
27 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Endocrinology & Metabolism
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