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

Melissa A. Merritt, Stefan Bentink, Matthew Schwede, Marcin P. Iwanicki, John Quackenbush, Terri Woo, Elin S. Agoston, Ferenc Reinhardt, Christopher P. Crum, Ross S. Berkowitz, Samuel C. Mok, Abigail E. Witt, Michelle A. Jones, Bin Wang, Tan A. Ince

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25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere80314
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 26 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Merritt, M. A., Bentink, S., Schwede, M., Iwanicki, M. P., Quackenbush, J., Woo, T., Agoston, E. S., Reinhardt, F., Crum, C. P., Berkowitz, R. S., Mok, S. C., Witt, A. E., Jones, M. A., Wang, B., & Ince, T. A. (2013). Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes. PloS one, 8(11), [e80314]. https://doi.org/10.1371/journal.pone.0080314