title: A Patient with an Extra-adrenal Pheochromocytoma and Germ-line SDHB Mutation Accompanied by an Atypical Meningioma.
abstract: The gene succinate dehydrogenase subunit B (SDHB) encodes a protein comprising part of the mitochondrial complex II, which links the Krebs cycle and the electron-transport chain. Heterozygous germ-line SDHB mutations causes familial pheochromocytoma-paraganglioma syndrome and has also been linked to gastrointestinal stromal tumors, as well as renal cell carcinomas. We herein report a patient with a germ-line SDHB mutation who presented with an atypical meningioma that was identified as originating from a somatic SDHB mutation. The 41-year-old man, who had a surgical history of extra-adrenal pheochromocytoma at 23 years of age, recently developed gait disorder and hypertension. At the radiological examination, a tumor was detected in the cervical spinal cord at the C6-7 intervertebral level. The pathological findings of the isolated tumor were atypical meningioma assessed as grade II according to the World Health Organization criteria. Inherited neoplasia syndrome was suspected because of the patient's history of early-onset extra-adrenal pheochromocytoma and the development of meningioma. We therefore performed molecular genetic analyses. A direct sequence analysis revealed a heterozygous germ-line frameshift mutation in SDHB, specifically an 11-nucleotide deletion, c.305-315delCAATGAACATC, in exon 4, resulting in a frameshift p.A102EfsX12. Additionally, the sequence analysis of the tumor DNA revealed only a mutated allele with a frameshift mutation in the germ-line SDHB. Our findings suggest that SDHB plays an important role in the pathogenesis of meningiomas as well as pheochromocytomas. Therefore, a differential diagnosis for metastatic pheochromocytoma and other new onset tumors, including meningioma, particularly in patients with germ-line SDHB mutations and a previous history of pheochromocytoma should be carefully made.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Tsuguka
authors.initials: T
authors.lastname: Shiwa
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoneda
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Haruya
authors.initials: H
authors.lastname: Ohno
authors.forename: Rui
authors.initials: R
authors.lastname: Kishimoto
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000483:Alleles; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D012186:Retroperitoneal Neoplasms / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C491545:SDHD protein, human; D013385:Succinate Dehydrogenase