title: Molecular genetic evidence for monoclonal origin of bilateral ovarian serous borderline tumors.
abstract: Patients with serous borderline tumors of the ovary often present with multiple tumors at different sites in the abdominal cavity. Whether different foci of ovarian serous borderline tumors are monoclonal in origin, arising as a consequence of spread from a single ovarian site, or whether such deposits are polyclonal and explained by independent molecular genetic alterations on the background of a field defect, is unknown. So far, only X-chromosome inactivation studies were performed to study this issue. We used a genome-wide allelotyping to assess clonality in 47 metachronous and/or synchronous multifocal tumors from 22 patients, using 59 microsatellite markers. Loss of heterozygosity (LOH) was observed in only 34 of 1969 informative markers in 9 of 22 serous borderline cases studied. Of these cases, 7 showed concordant LOH for at least one polymorphic marker in more than one tumor site. Flanking microsatellite markers enabled identification of identical chromosomal breakpoints in 6 of 7 cases. The LOH results strongly favor a common origin indicated by a likelihood ratio (possibility common origin/possibility independent origin) ranging from 39 to 14,163. Strong additional evidence for monoclonality is provided by the finding of identical microsatellite alterations in all three-tumor sites in one case.
authors.affiliation: Department of Pathology, the University Medical Center, Leiden, The Netherlands.
authors.forename: Nathalie L G
authors.initials: NL
authors.lastname: Sieben
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Kolkman-Uljee
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
mesh_terms: D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D005260:Female; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011336:Probability
chemical_list: D005819:Genetic Markers