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Clonal Origin of Epithelial Ovarian Carcinoma: Analysis by Loss of Heterozygosity, p53 Mutation, and X-Chromosome Inactivation
- Source :
- JNCI Journal of the National Cancer Institute. 84:1793-1798
- Publication Year :
- 1992
- Publisher :
- Oxford University Press (OUP), 1992.
-
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. PURPOSE: 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. IMPLICATIONS: 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.
- Subjects :
- Heterozygote
Cancer Research
Pathology
medicine.medical_specialty
Ovary
Biology
Gene mutation
medicine.disease_cause
X-inactivation
Loss of heterozygosity
Dosage Compensation, Genetic
medicine
Humans
Alleles
Ovarian Neoplasms
Mutation
Carcinoma
Cancer
DNA, Neoplasm
Genes, p53
medicine.disease
Clone Cells
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
Monoclonal
Female
Ovarian cancer
Subjects
Details
- ISSN :
- 14602105 and 00278874
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- JNCI Journal of the National Cancer Institute
- Accession number :
- edsair.doi.dedup.....09338f36299d0c063b709957c75e8da4
- Full Text :
- https://doi.org/10.1093/jnci/84.23.1793