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  • Oncogenomics
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Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients

Oncogene volume 21, pages 7605–7608 (2002)Cite this article

Abstract

Allelic loss of the long arm of chromosome 11 is frequent in neuroendocrine tumors (NET) of different organs. However, the MEN1 gene on 11q13 is mutated only in a subset of NET and allelic losses on 11q frequently extend to the telomere. In this genetic region lies the tumor suppressor gene SDHD which is associated with hereditary paragangliomas (PGL1). We sought to determine whether SDHD plays a role in the development of sporadic NET. By mutation and deletion analysis of SDHD we were unable to detect any SDHD mutation in 45 NET of the lung, gastrointestinal tract, pancreas or parathyroid. However, we found allelic deletions in 20 to 50% of all tumors but parathyroid adenomas. Furthermore, we found heterozygous germline variants in 2/8 paragangliomas. A first case of variant c.149 A>G (H50R) was found in a patient with an extra-adrenal pheochromocytoma, the other variant c.34 G>A (G12S) in a patient with a paratracheal paraganglioma, C-cell hyperplasia of the thyroid and hyperplasia of ACTH-producing cells of the pituitary gland. Both variants were absent in 93 controls. Our results demonstrate that somatic SDHD mutations are rare in sporadic NET. However, LOH alone could lead to a complete loss of function since SDHD is an imprinted gene. Furthermore, we describe two germline variants possibly causing hereditary paragangliomas.

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Acknowledgements

Supported by Swiss Cancer League grant SKL-997-02-2000 and Swiss National Science Foundation grant 31-618845.00.

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Authors and Affiliations

  1. Department of Pathology, University Hospital, Zurich, 8091, Switzerland

    Aurel Perren, André Barghorn, Sonja Schmid, Parvin Saremaslani, Jürgen Roth & Philipp U Heitz

  2. Institue of Pathology, Baden, 5404, Switzerland

    Paul Komminoth

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  1. Aurel Perren
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  2. André Barghorn
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Correspondence to Aurel Perren.

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Perren, A., Barghorn, A., Schmid, S. et al. Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients. Oncogene 21, 7605–7608 (2002). https://doi.org/10.1038/sj.onc.1205812

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