Cedars-sinai Medical Center

Beth Y Karlan

Clive N Svendsen

Xiaojiang Cui

Nur Yucer

Tilly Jenkins Vogel

Zhenqiu Liu

Dong-Joo Cheon

Sandra Orsulic

Marie Holzapfel

Mourad Tighiouart

Xiaojian Cui

The fallopian tube epithelium (FTE) has been recognized as a site of origin of high-grade serous ovarian cancer (HGSC). However, absence of relevant in vitro human models that can recapitulate tissue-specific architecture has hindered understanding of FTE transformation and initiation of HGSC. Here, induced pluripotent stem cells (iPSCs) were used to establish a novel 3-dimensional (3D) human FTE organoid in vitro model containing the relevant cell types of the human fallopian tube as well as a luminal architecture that closely reflects the organization of fallopian tissues in vivo. Modulation of Wnt and nodal/activin signaling pathways provided iPSC differentiation into M&#xfc;llerian cells and subsequent use of pro-M&#xfc;llerian growth factors promoted FTE precursors. The expression of M&#xfc;llerian markers verified correct cellular differentiation. An innovative 3D growth platform, which enabled the FTE organoid to self-organize into a convoluted luminal structure, permitted final differentiation to a FTE lineage. This powerful human-derived FTE organoid model can be used to study the earliest stages of HGSC development and to identify novel and specific biomarkers of early fallopian tube epithelial cell transformation.

Methods and compositions for production of fallopian tube epithelium

Described herein are gene signatures providing prognostic, diagnostic, treatment and molecular subtype classifications of ovarian cancers through generation of ovarian cancer disease signatures (OCDSs) that account for molecular heterogeneity present in gynecological cancers. An ovarian cancer fixed signature (OCFS) is described which relates to the core programming of disease development, in addition to an ovarian cancer stem cell (OCSC) signature. Development various disease signature, suggests personalized treatment strategies focused on molecular subtypes of gynecological cancers, such as triage tests for patients.

Molecular signatures of ovarian cancer

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Los Angeles, CA, United States of America

Beth Y Karlan