Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad

Haller F, Moskalev E, Faucz FR, Barthelmeß S, Wiemann S, Bieg M, Assie G, Bertherat J, Schaefer IM, Otto C, Rattenberry E, Maher ER, Stroebel P, Werner M, Carney JA, Hartmann A, Stratakis CA, Agaimy A (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Endocrine-Related Cancer BioScientifica

Book Volume: 21

Pages Range: 567-77

Journal Issue: 4

DOI: 10.1530/ERC-14-0254

Abstract

Carney triad (CT) is a rare condition with synchronous or metachronous occurrence of gastrointestinal stromal tumors (GISTs), paragangliomas (PGLs), and pulmonary chondromas in a patient. In contrast to Carney-Stratakis syndrome (CSS) and familial PGL syndromes, no germline or somatic mutations in the succinate dehydrogenase (SDH) complex subunits A, B, C, or D have been found in most tumors and/or patients with CT. Nonetheless, the tumors arising among patients with CT, CSS, or familial PGL share a similar morphology with loss of the SDHB subunit on the protein level. For the current study, we employed massive parallel bisulfite sequencing to evaluate DNA methylation patterns in CpG islands in proximity to the gene loci of all four SDH subunits. For the first time, we report on a recurrent aberrant dense DNA methylation at the gene locus of SDHC in tumors of patients with CT, which was not present in tumors of patients with CSS or PGL, or in sporadic GISTs with KIT mutations. This DNA methylation pattern was correlated to a reduced mRNA expression of SDHC, and concurrent loss of the SDHC subunit on the protein level. Collectively, these data suggest epigenetic inactivation of the SDHC gene locus with functional impairment of the SDH complex as a plausible alternate mechanism of tumorigenesis in CT.

Authors with CRIS profile

Evgeny Moskalev Institute of Pathology Sarah Barthelmeß Professur für Diagnostische Molekularpathologie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

US National Institutes of Health (NIH) US United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) University of Paris 5 - René Descartes / Université Paris V René Descartes FR France (FR) Georg-August-Universität Göttingen DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Birmingham Women's and Children's NHS Foundation Trust GB United Kingdom (GB) Mayo Clinic US United States (USA) (US)

How to cite

APA:

Haller, F., Moskalev, E., Faucz, F.R., Barthelmeß, S., Wiemann, S., Bieg, M.,... Agaimy, A. (2014). Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad. Endocrine-Related Cancer, 21(4), 567-77. https://doi.org/10.1530/ERC-14-0254

MLA:

Haller, Florian, et al. "Aberrant DNA hypermethylation of SDHC: a novel mechanism of tumor development in Carney triad." Endocrine-Related Cancer 21.4 (2014): 567-77.

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