Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes

The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e80314-e80314
Main Authors: Merritt, Melissa A, Bentink, Stefan, Schwede, Matthew, Iwanicki, Marcin P, Quackenbush, John, Woo, Terri, Agoston, Elin S, Reinhardt, Ferenc, Crum, Christopher P, Berkowitz, Ross S, Mok, Samuel C, Witt, Abigail E, Jones, Michelle A, Wang, Bin, Ince, Tan A
Format: Article
Language:English
Subjects:
Animals
Breast cancer
Cancer
Cell culture
Cell Line, Transformed
Disease Models, Animal
Epithelial cells
Epithelial Cells - metabolism
Fallopian tube
Fallopian Tubes - metabolism
Female
Gene expression
Gene Expression Profiling
Heterografts
Humans
Mice
Mutation
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - mortality
Ovarian Neoplasms - pathology
Ovary - metabolism
Pathology
Primary Cell Culture
Prognosis
Subgroups
Transcriptome
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Summary:The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV) and fallopian tube (FT) epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080314