{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T05:06:18Z","timestamp":1703653578938},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World j. surg."],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pheochromocytomas (PCCs) develop from the adrenal medulla and are often part of a hereditary syndrome such as von Hippel\u2013Lindau (VHL) syndrome. In VHL, only about 30 % of patients with a <jats:italic>VHL<\/jats:italic> missense mutation develop PCCs. Thus, additional genetic events leading to formation of such tumors in patients with VHL syndrome are sought. <jats:italic>SDHAF2<\/jats:italic> (previously termed <jats:italic>SDH5<\/jats:italic>) and <jats:italic>SDHD<\/jats:italic> are both located on chromosome 11q and are required for the function of mitochondrial complex II. While <jats:italic>SDHAF2<\/jats:italic> has been shown to be mutated in patients with paragangliomas (PGLs), <jats:italic>SDHD<\/jats:italic> mutations have been found both in patients with PCCs and in patients with PGLs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Because loss of 11q is a common event in VHL\u2010associated PCCs, we aimed to investigate whether <jats:italic>SDHAF2<\/jats:italic> and <jats:italic>SDHD<\/jats:italic> are targets. In the present study, 41 VHL\u2010associated PCCs were screened for mutations and loss of heterozygosity (LOH) in <jats:italic>SDHAF2<\/jats:italic> or <jats:italic>SDHD<\/jats:italic>. Promoter methylation, as well as mRNA expression of <jats:italic>SDHAF2<\/jats:italic> and <jats:italic>SDHD<\/jats:italic>, was studied. In addition, immunohistochemistry (IHC) of <jats:italic>SDHB<\/jats:italic>, known to be a universal marker for loss of any part the SDH complex, was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusions<\/jats:title><jats:p>LOH was found in more than 50 % of the VHL\u2010associated PCCs, and was correlated with a significant decrease (<jats:italic>p<\/jats:italic> &lt; 0.05) in both <jats:italic>SDHAF2<\/jats:italic> and <jats:italic>SDHD<\/jats:italic> 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 <jats:italic>SDHAF2\/SDHD<\/jats:italic> mRNA expression. In addition, the lack of mutations and promoter methylation in the investigated samples indicates that other events on chromosome 11\u00a0might be involved in the development of PCCs in association with VHL syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00268-013-2373-2","type":"journal-article","created":{"date-parts":[[2013,12,9]],"date-time":"2013-12-09T20:31:35Z","timestamp":1386621095000},"page":"724-732","source":"Crossref","is-referenced-by-count":6,"title":["Role of <i>SDHAF2<\/i> and <i>SDHD<\/i> in von Hippel\u2013Lindau Associated Pheochromocytomas"],"prefix":"10.1002","volume":"38","author":[{"given":"Johan","family":"Kugelberg","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Welander","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Schiavi","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic Veneto Institute of Oncology IRCCS Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ambrogio","family":"Fassina","sequence":"additional","affiliation":[{"name":"Surgical Pathology &amp; Cytopathology Unit, Department of Medicine (DIMED) University of Padua Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"B\u00e4ckdahl","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"Larsson","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet, CCK Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Opocher","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic Veneto Institute of Oncology IRCCS Padua Italy"},{"name":"Department of Medicine (DIMED) University of Padua Padua Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"S\u00f6derkvist","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health Sciences Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia L.","family":"Dahia","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cancer Therapy and Research Center University of Texas Health Science Center San Antonio TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut P. 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