Genetic analysis of the early natural history of epithelial ovarian carcinoma.

<h4>Background</h4>The high mortality rate associated with epithelial ovarian carcinoma (EOC) reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy.<h4>Metho...

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Autores principales: Bhavana Pothuri, Mario M Leitao, Douglas A Levine, Agnès Viale, Adam B Olshen, Crispinita Arroyo, Faina Bogomolniy, Narciso Olvera, Oscar Lin, Robert A Soslow, Mark E Robson, Kenneth Offit, Richard R Barakat, Jeff Boyd
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:0a051a1d3a2641e4a0d8b50c277be9a92021-12-02T20:22:07ZGenetic analysis of the early natural history of epithelial ovarian carcinoma.1932-620310.1371/journal.pone.0010358https://doaj.org/article/0a051a1d3a2641e4a0d8b50c277be9a92010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20436685/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The high mortality rate associated with epithelial ovarian carcinoma (EOC) reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy.<h4>Methodology/principal findings</h4>Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis) was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium.<h4>Conclusions/significance</h4>Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.Bhavana PothuriMario M LeitaoDouglas A LevineAgnès VialeAdam B OlshenCrispinita ArroyoFaina BogomolniyNarciso OlveraOscar LinRobert A SoslowMark E RobsonKenneth OffitRichard R BarakatJeff BoydPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10358 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Bhavana Pothuri
Mario M Leitao
Douglas A Levine
Agnès Viale
Adam B Olshen
Crispinita Arroyo
Faina Bogomolniy
Narciso Olvera
Oscar Lin
Robert A Soslow
Mark E Robson
Kenneth Offit
Richard R Barakat
Jeff Boyd
Genetic analysis of the early natural history of epithelial ovarian carcinoma.
description <h4>Background</h4>The high mortality rate associated with epithelial ovarian carcinoma (EOC) reflects diagnosis commonly at an advanced stage, but improved early detection is hindered by uncertainty as to the histologic origin and early natural history of this malignancy.<h4>Methodology/principal findings</h4>Here we report combined molecular genetic and morphologic analyses of normal human ovarian tissues and early stage cancers, from both BRCA mutation carriers and the general population, indicating that EOCs frequently arise from dysplastic precursor lesions within epithelial inclusion cysts. In pathologically normal ovaries, molecular evidence of oncogenic stress was observed specifically within epithelial inclusion cysts. To further explore potential very early events in ovarian tumorigenesis, ovarian tissues from women not known to be at high risk for ovarian cancer were subjected to laser catapult microdissection and gene expression profiling. These studies revealed a quasi-neoplastic expression signature in benign ovarian cystic inclusion epithelium compared to surface epithelium, specifically with respect to genes affecting signal transduction, cell cycle control, and mitotic spindle formation. Consistent with this gene expression profile, a significantly higher cell proliferation index (increased cell proliferation and decreased apoptosis) was observed in histopathologically normal ovarian cystic compared to surface epithelium. Furthermore, aneuploidy was frequently identified in normal ovarian cystic epithelium but not in surface epithelium.<h4>Conclusions/significance</h4>Together, these data indicate that EOC frequently arises in ovarian cystic inclusions, is preceded by an identifiable dysplastic precursor lesion, and that increased cell proliferation, decreased apoptosis, and aneuploidy are likely to represent very early aberrations in ovarian tumorigenesis.
format article
author Bhavana Pothuri
Mario M Leitao
Douglas A Levine
Agnès Viale
Adam B Olshen
Crispinita Arroyo
Faina Bogomolniy
Narciso Olvera
Oscar Lin
Robert A Soslow
Mark E Robson
Kenneth Offit
Richard R Barakat
Jeff Boyd
author_facet Bhavana Pothuri
Mario M Leitao
Douglas A Levine
Agnès Viale
Adam B Olshen
Crispinita Arroyo
Faina Bogomolniy
Narciso Olvera
Oscar Lin
Robert A Soslow
Mark E Robson
Kenneth Offit
Richard R Barakat
Jeff Boyd
author_sort Bhavana Pothuri
title Genetic analysis of the early natural history of epithelial ovarian carcinoma.
title_short Genetic analysis of the early natural history of epithelial ovarian carcinoma.
title_full Genetic analysis of the early natural history of epithelial ovarian carcinoma.
title_fullStr Genetic analysis of the early natural history of epithelial ovarian carcinoma.
title_full_unstemmed Genetic analysis of the early natural history of epithelial ovarian carcinoma.
title_sort genetic analysis of the early natural history of epithelial ovarian carcinoma.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/0a051a1d3a2641e4a0d8b50c277be9a9
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