title: Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?
abstract: BACKGROUND
  Hepatoblastoma (HB) is the most frequent liver tumor in childhood, occurring in the first few years of life. Surgery combined with chemotherapy has resulted in dramatic improvements in prognosis. However, even today, about one quarter of affected children do not survive the disease. Compared to the general population, the risk of HB is 750-7,500 times higher in children predisposed to familial adenomatous polyposis (FAP), an autosomal-dominant cancer predispostion syndrome caused by germline mutations in the tumor suppressor gene APC. Only limited data exist about the frequency of APC germline mutations in cases of apparently sporadic HB without a family history of FAP.
  
  
  METHODS
  In our sample of 1,166 German FAP families, all known cases of HB were registered. In addition, 50 patients with apparently sporadic HB were examined for APC germline mutations.
  
  
  RESULTS
  In the FAP families, seven unrelated cases of HB are documented; three had been detected at an advanced stage. In patients with apparently sporadic HB, germline mutations in the APC gene were identified in 10%.
  
  
  CONCLUSIONS
  These data raise the issue of the appropriate screening for HB in children of FAP patients. To date, the efficiency of surveillance for HB is unclear. In Beckwith-Wiedemann syndrome (BWS), recent studies suggest an earlier detection of both Wilms tumor and HB by frequent screening. We discuss the rationale and implications of a screening program; besides the examination procedure itself, screening for HB in children of FAP patients would have important consequences for the policy of predictive testing in FAP. In a substantial fraction of sporadic HB, the disease is obviously the first manifestation of a de novo FAP. These patients should be identified by routine APC mutation screening and undergo colorectal surveillance thereafter.
authors.affiliation: Institute of Human Genetics, University of Bonn, Wilhelmstrasse, Bonn, Germany. Stefan.Aretz@ukb.uni-bonn.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.forename: Siegfried
authors.initials: S
authors.lastname: Uhlhaas
authors.forename: Waltraut
authors.initials: W
authors.lastname: Friedl
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Dietrich
authors.initials: D
authors.lastname: von Schweinitz
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D005091:Exons; D005500:Follow-Up Studies; D017491:Genes, APC; D005820:Genetic Testing; D018095:Germ-Line Mutation; D018197:Hepatoblastoma / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009367:Neoplasm Staging; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate