liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Role of SDHAF2 and SDHD in von Hippel-Lindau Associated Pheochromocytomas
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Veneto Institute Oncology IRCCS, Italy .
University of Padua, Italy .
Show others and affiliations
2014 (English)In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 38, no 3, 724-732 p.Article in journal (Refereed) Published
Abstract [en]

Background Pheochromocytomas (PCCs) develop from the adrenal medulla and are often part of a hereditary syndrome such as von Hippel-Lindau (VHL) syndrome. In VHL, only about 30 % of patients with a VHL missense mutation develop PCCs. Thus, additional genetic events leading to formation of such tumors in patients with VHL syndrome are sought. SDHAF2 (previously termed SDH5) and SDHD are both located on chromosome 11q and are required for the function of mitochondrial complex II. While SDHAF2 has been shown to be mutated in patients with paragangliomas (PGLs), SDHD mutations have been found both in patients with PCCs and in patients with PGLs. Materials and methods Because loss of 11q is a common event in VHL-associated PCCs, we aimed to investigate whether SDHAF2 and SDHD are targets. In the present study, 41 VHL-associated PCCs were screened for mutations and loss of heterozygosity (LOH) in SDHAF2 or SDHD. Promoter methylation, as well as mRNA expression of SDHAF2 and SDHD, was studied. In addition, immunohistochemistry (IHC) of SDHB, known to be a universal marker for loss of any part the SDH complex, was conducted. Results and conclusions LOH was found in more than 50 % of the VHL-associated PCCs, and was correlated with a significant decrease (p less than 0.05) in both SDHAF2 and SDHD mRNA expression, which may be suggestive of a pathogenic role. However, while SDHB protein expression as determined by IHC in a small cohort of tumors was lower in PCCs than in the surrounding adrenal cortex, there was no obvious correlation with LOH or the level of SDHAF2/SDHD mRNA expression. In addition, the lack of mutations and promoter methylation in the investigated samples indicates that other events on chromosome 11 might be involved in the development of PCCs in association with VHL syndrome.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2014. Vol. 38, no 3, 724-732 p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-106102DOI: 10.1007/s00268-013-2373-2ISI: 000333151700030OAI: diva2:714189
Available from: 2014-04-25 Created: 2014-04-24 Last updated: 2015-04-10

Open Access in DiVA

fulltext(1368 kB)169 downloads
File information
File name FULLTEXT01.pdfFile size 1368 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Welander, JennySöderkvist, PeterGimm, Oliver
By organisation
Department of Clinical and Experimental MedicineFaculty of Health SciencesDivision of Cell BiologyDepartment of Clinical Pathology and Clinical GeneticsDivision of Clinical SciencesDepartment of Surgery in Linköping
In the same journal
World Journal of Surgery
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 169 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 101 hits
ReferencesLink to record
Permanent link

Direct link