title: Molecular genetic analysis of bilateral ovarian germ cell tumors.
abstract: BACKGROUND
  Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous with regard to their clinical and histologic appearance. The risk of tumor development is higher in children with aberrant sexual differentiation. Development of gonadoblastomas is seen in young women with 46,XY gonadal dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs, mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically inapparent patients for sex chromosomal aberrations.
  
  
  METHODS
  We analyzed tumor samples of 15 patients with synchronous bilateral oGCTs enrolled onto the consecutive MAKEI trials for non-testicular GCTs. Paraffin embedded samples from the Kiel German Childhood Tumor Registry were evaluated for the presence of Y-chromosomal sequences. Molecular genetic techniques included comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization.
  
  
  RESULTS
  Among 15 patients with bilateral oGCTs, Y-chromosomal DNA sequences were detected in 6 tumors. Both mature teratomas were negative for Y-chromosomal DNA. Thus, 5 of 12 malignant oGCTs and 1 immature teratoma (with elevated AFP) showed Y-chromosomal material. A 45(X,0) karyotype could not be demonstrated.
  
  
  CONCLUSIONS
  These investigations provide additional insight into the development of oGCTs: mature teratomas, which develop from postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y-chromosomal DNA, indicating underlying but clinically inapparent gonadal dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be involved in tumor development in about half of these patients.
authors.affiliation: Clinic of Pediatric Oncology, Hematology and Immunology, Heinrich--Heine-University, Düsseldorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Hennes
authors.forename: S
authors.initials: S
authors.lastname: Zahn
authors.forename: L F
authors.initials: LF
authors.lastname: Lopes
authors.forename: S
authors.initials: S
authors.lastname: Schönberger
authors.forename: I
authors.initials: I
authors.lastname: Leuschner
authors.forename: U
authors.initials: U
authors.lastname: Göbel
authors.forename: G
authors.initials: G
authors.lastname: Calaminus
authors.forename: D T
authors.initials: DT
authors.lastname: Schneider
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D041322:Chromosomes, Human, Y / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004407:Dysgerminoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D005260:Female; D005858:Germany; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D010053:Ovary / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013724:Teratoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D055815:Young Adult