title: Prevalence of germline mutations in patients with pheochromocytoma or abdominal paraganglioma and sporadic presentation: a population-based study in Western Sweden.
abstract: BACKGROUND
  Germline mutations in the susceptibility genes RET, SDHB, SDHD, and VHL have been reported in 7.5-24% of patients with pheochromocytoma (Pheo) or paraganglioma (PGL) and sporadic presentation. The purpose of the present study was to establish population-based data on the frequency of germline mutations in patients with apparently sporadic Pheo or abdominal PGL in Western Sweden.
  
  
  METHODS
  From the Swedish National Cancer Registry, all patients with Pheo or PGL in Western Sweden (population 1.72 million) registered between 1958 and 2009 were identified (n = 256). Patients were characterized using register data, hospital records, and clinical interviews. All living patients with Pheo or abdominal PGL and sporadic presentation (n = 81) were invited to genetic screening; 71 patients accepted. Germline mutations were investigated by using direct sequencing for point mutations in RET, SDHB, SDHD, and VHL, and multiplex ligation-dependent probe amplification for gross deletions in SDHB, SDHC, SDHD, and VHL. Plasma or urinary metanephrines and/or urinary catecholamines were used for biochemical follow-up.
  
  
  RESULTS
  The prevalence of germline mutations was 5.6%. Mutations were only seen in RET (n = 1) and SDHB (n = 3). Notably, in the patients with SDHB mutations, no malignant phenotype was observed during a mean follow-up of 23.3 years.
  
  
  CONCLUSIONS
  The frequency of germline mutations in patients with apparently sporadic Pheo and abdominal PGL in Western Sweden was lower than in previous studies. Variations in reported frequencies of germline mutations in patients with clinically sporadic Pheo/PGL may reflect geographical differences or patient selection.
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden. andreas.muth@vgregion.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Muth
authors.forename: Frida
authors.initials: F
authors.lastname: Abel
authors.forename: Svante
authors.initials: S
authors.lastname: Jansson
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlman
authors.forename: Bo
authors.initials: B
authors.lastname: Wängberg
mesh_terms: D000008:Abdominal Neoplasms / Q000235:genetics*; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics*; D010507:Periodicity; D010673:Pheochromocytoma / Q000235:genetics*; D017354:Point Mutation; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012042:Registries; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013385:Succinate Dehydrogenase / Q000235:genetics; D013548:Sweden; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human