title: Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation.
abstract: BACKGROUND
  It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer.
  
  
  OBJECTIVE
  The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin.
  
  
  METHODS
  DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at five loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene.
  
  
  RESULTS
  In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors.
  
  
  CONCLUSIONS
  The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin.
  
  
  CONCLUSIONS
  These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: I J
authors.initials: IJ
authors.lastname: Jacobs
authors.forename: M F
authors.initials: MF
authors.lastname: Kohler
authors.forename: R W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: J R
authors.initials: JR
authors.lastname: Marks
authors.forename: R
authors.initials: R
authors.lastname: Whitaker
authors.forename: B A
authors.initials: BA
authors.lastname: Kerns
authors.forename: P
authors.initials: P
authors.lastname: Humphrey
authors.forename: A
authors.initials: A
authors.lastname: Berchuck
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
authors.forename: R C
authors.initials: RC
authors.lastname: Bast
mesh_terms: D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells / Q000502:physiology*; D004273:DNA, Neoplasm / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm