title: Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes.
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.
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America ; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Matthew
authors.initials: M
authors.lastname: Schwede
authors.forename: Marcin P
authors.initials: MP
authors.lastname: Iwanicki
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Terri
authors.initials: T
authors.lastname: Woo
authors.forename: Elin S
authors.initials: ES
authors.lastname: Agoston
authors.forename: Ferenc
authors.initials: F
authors.lastname: Reinhardt
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
authors.forename: Ross S
authors.initials: RS
authors.lastname: Berkowitz
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Mok
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Witt
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Jones
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Tan A
authors.initials: TA
authors.lastname: Ince
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D005187:Fallopian Tubes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010053:Ovary / Q000378:metabolism*; D061251:Primary Cell Culture; D011379:Prognosis; D059467:Transcriptome