title: Novel germline mutations in the SDHB and SDHD genes in Japanese pheochromocytomas.
abstract: The SDHA, SDHB, SDHC, and SDHD genes code for subunits of succinate dehydrogenase (SDH), which forms part of the mitochondrial respiratory chain. Germline mutations in the genes encoding SDHB and SDHD have been reported in familial paragangliomas/pheochromocytomas and in apparently sporadic pheochromocytomas. SDHB and SDHD mutations are widely distributed along the genes with no apparent hot spots. SDHB mutations are often detected in malignant and extra-adrenal pheochromocytomas. SDHD mutations are also detected frequently in head and neck paragangliomas. We sequenced the entire coding regions of the SDHB and SDHD genes in 17 pheochromocytomas. We identified novel heterozygous G to A point mutations at the first base of intron 3 of the SDHB gene in a malignant extra-adrenal abdominal pheochromocytoma patient, and at the first base of codon 111 of the SDHD gene in an adrenal pheochromocytoma patient. Further, we confirmed the SDHD mutation by DHPLC. The prevalence of SDHB and SDHD mutations in pheochromocytomas we examined was 12% (2/17). Thus, we identified two novel SDH mutations in Japanese pheochromocytomas. Further studies will investigate the oncogenic potential of these mutations.
authors.affiliation: Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. k-isobe@md.tsukuba.ac.jp
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Isobe
authors.forename: Shigeru
authors.initials: S
authors.lastname: Minowada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Sumiko
authors.initials: S
authors.lastname: Nissato
authors.forename: Toru
authors.initials: T
authors.lastname: Nanmoku
authors.forename: Hisato
authors.initials: H
authors.lastname: Hara
authors.forename: Toru
authors.initials: T
authors.lastname: Yashiro
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takekoshi
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D007506:Iron-Sulfur Proteins; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase