title: Clonal analysis favours a monoclonal origin for serous borderline tumours with peritoneal implants.
abstract: Serous borderline tumours (SBTs) of the ovary were originally classified as such because the vast majority behave in a remarkably indolent manner, even in the presence of widespread tumour deposits, termed implants, and/or lymph node involvement. The pathogenesis of the implants is currently unknown. Two major hypotheses have been proposed: the first favours a monoclonal origin, arguing that the peritoneal lesions derive from neoplastic cells that are shed from the primary ovarian tumour. The second hypothesis favours a polyclonal origin as a result of a field defect of susceptible Müllerian cells from which multiple independent tumours arise. To test both hypotheses, genome-wide allelotyping and B-RAF/K-RAS mutation analyses were employed to assess clonality in 25 metachronous or synchronous tumours from ten SBT patients. Loss of heterozygosity (LOH) profiling and K-RAS/B-RAF mutation analysis showed concordance of the genetic changes in all sites in 21 tumours from eight patients who were informative. These results favour a common origin, underscored by a likelihood ratio (probability of common origin/probability of independent origin) ranging from 2.43 to 7,662,850. In conclusion, this study strongly supports the hypothesis that both non-invasive and invasive implants arise as a consequence of spread from a single ovarian site.
authors.affiliation: Department of Pathology, University of Maastricht, The Netherlands.
authors.forename: N L
authors.initials: NL
authors.lastname: Sieben
authors.forename: G M J M
authors.initials: GM
authors.lastname: Roemen
authors.forename: J
authors.initials: J
authors.lastname: Oosting
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: M
authors.initials: M
authors.lastname: van Engeland
authors.forename: J
authors.initials: J
authors.lastname: Prat
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology; D010537:Peritoneum / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf