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Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer
Department of Translational Medicine and Diagnostics, Morphotek, Inc., 210 Welsh Pool Rd., Exton, PA 19341, USA
Biomarkers and Personalized Medicine Core Functional Unit, Eisai Inc., Four Corporate Drive, Andover, MA 01810,USA
* Author to whom correspondence should be addressed.
Received: 9 April 2013; in revised form: 18 June 2013 / Accepted: 20 June 2013 / Published: 1 July 2013
Abstract: Folate receptor alpha (FOLR1/FRA) is reported to be overexpressed in epithelial ovarian cancers (EOC), especially the serous histotype. Further, while dysregulation of the folate-dependent 1-carbon cycle has been implicated in tumorogenesis, little is known relative to the potential mechanism of action of FOLR1 expression in these processes. We therefore investigated the expression of FOLR1, other folate receptors, and genes within the 1-carbon cycle in samples of EOC, normal ovary and fallopian tube on a custom TaqMan Low Density Array. Also included on this array were known markers of EOC such as MSLN, MUC16 and HE4. While few differences were observed in the expression profiles of genes in the 1-carbon cycle, genes previously considered to be overexpressed in EOC (e.g., FOLR1, MSLN, MUC16 and HE4) showed significantly increased expression when comparing EOC to normal ovary. However, when the comparator was changed to normal fallopian tube, these differences were abolished, supporting the hypothesis that EOC derives from fallopian fimbriae and, further, that markers previously considered to be upregulated or overexpressed in EOC are most likely not of ovarian origin, but fallopian in derivation. Our findings therefore support the hypothesis that the cell of origin of EOC is tubal epithelium.
Keywords: folate receptor alpha; FRA; ovarian cancer; fallopian tube; 1-carbon metabolism; reduced folate carrier; methylation
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O'Shannessy, D.J.; Jackson, S.M.; Twine, N.C.; Hoffman, B.E.; Dezso, Z.; Agoulnik, S.I.; Somers, E.B. Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer. Int. J. Mol. Sci. 2013, 14, 13687-13703.
O'Shannessy DJ, Jackson SM, Twine NC, Hoffman BE, Dezso Z, Agoulnik SI, Somers EB. Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer. International Journal of Molecular Sciences. 2013; 14(7):13687-13703.
O'Shannessy, Daniel J.; Jackson, Stephen M.; Twine, Natalie C.; Hoffman, Bryan E.; Dezso, Zoltan; Agoulnik, Sergei I.; Somers, Elizabeth B. 2013. "Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer." Int. J. Mol. Sci. 14, no. 7: 13687-13703.