title: Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot?
abstract: Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise in the adrenal medulla and the extra-adrenal paraganglia, respectively. Inheritance of these tumors is mainly a result of mutations affecting the VHL, RET, NF1, and SDH genes. Germ-line mutations of the SDH genes have been found to account for nearly 10% of apparently sporadic cases. Nevertheless, alterations other than point mutations have not yet been well characterized. In this study, we investigated the frequency of gross SDH deletions in 24 patients who tested negative for point mutations and had at least one of the recommended features for genetic testing. For this purpose, we used a technique that is easy to implement in the lab to specifically detect gross deletions affecting SDHB, SDHC, and SDHD. We identified 3 heterozygous SDHB deletions (3/24) in 3 independent cases with paraganglioma: 1 whole SDHB deletion and 2 deletions exclusively affecting exon 1. These latter mutations match the unique gross deletion previously reported, indicating this region could be a hot spot for gross SDHB deletions. It seems likely that these alterations can account for a considerable number of both familial and apparently sporadic paraganglioma cases. Although this is the first report describing the presence of gross deletions in patients with apparently sporadic paragangliomas, the extra-adrenal location of the tumor seems to constitute a determining factor for whether to include these patients in genetic testing for gross deletions in the SDHB gene.
authors.affiliation: Hereditary Endocrine Cancer Group, Centro Nacional de Investigaciones Oncoloógicas, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascón
authors.forename: Cristina
authors.initials: C
authors.lastname: Montero-Conde
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz-Llorente
authors.forename: Fátima
authors.initials: F
authors.lastname: Mercadillo
authors.forename: Rocío
authors.initials: R
authors.lastname: Letón
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez-Antona
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Delgado
authors.forename: Manuel
authors.initials: M
authors.lastname: Delgado
authors.forename: Alberto
authors.initials: A
authors.lastname: Díez
authors.forename: Adela
authors.initials: A
authors.lastname: Rovira
authors.forename: José Angel
authors.initials: JA
authors.lastname: Díaz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D005091:Exons; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D007438:Introns; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D017354:Point Mutation; D021122:Protein Subunits / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C108096:SDHC protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase