title: Molecular evidence linking primary cancer of the fallopian tube to BRCA1 germline mutations.
abstract: OBJECTIVE
  BRCA1 and BRCA2 germline mutations increase the risk of ovarian and breast cancer. Fallopian tube cancer has occasionally been observed in breast-ovarian cancer families. At our family cancer clinic we recently encountered two cases of Fallopian tube cancer within two families harboring a BRCA1 germline mutation. To study the relationship between Fallopian tube cancer and BRCA1 mutations, a histopathological reevaluation and molecular analysis were performed.
  
  
  METHODS
  Medical and histopathological reports of the Fallopian tube cancer cases as well as archival tissue blocks were retrieved. The histopathological diagnoses were reevaluated. We investigated whether patients with Fallopian tube cancer had been carriers of a BRCA germline mutation. In addition we investigated whether loss of the wild-type allele had occurred in the tumor.
  
  
  RESULTS
  In 2 of 23 families with a known BRCA1 mutation from our family cancer clinic, a case of Fallopian tube cancer was reported. Histological reevaluation confirmed the diagnosis of Fallopian tube cancer in both cases. In one case Fallopian tube cancer may have been part of a multifocal primary malignancy. In both patients the presence of a BRCA1 mutation was confirmed in the germline. Furthermore, we showed loss of the wild-type BRCA1 allele in both tumors.
  
  
  CONCLUSIONS
  These findings provide the first molecular evidence that Fallopian tube cancer may be due to germline mutations in BRCA1. This may have important consequences for the preferred method of prophylactic oophorectomy in BRCA1 mutation carriers.
authors.affiliation: Family Cancer Clinic, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Zweemer
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: R H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: A
authors.initials: A
authors.lastname: Ryan
authors.forename: J J
authors.initials: JJ
authors.lastname: Gille
authors.forename: R H
authors.initials: RH
authors.lastname: Sijmons
authors.forename: I J
authors.initials: IJ
authors.lastname: Jacobs
authors.forename: F H
authors.initials: FH
authors.lastname: Menko
authors.forename: P
authors.initials: P
authors.lastname: Kenemans
mesh_terms: D000328:Adult; D000368:Aged; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D011379:Prognosis; D018570:Risk Assessment