Cell reports · 2019
A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Lawrenson Kate, Fonseca Marcos A S, Liu Annie Y, Segato Dezem Felipe, Lee Janet M, Lin Xianzhi, Corona Rosario I, Abbasi Forough, Vavra Kevin C, Dinh Huy Q, Gill Navjot Kaur, Seo Ji-Heui, Coetzee Simon, Lin Yvonne G, Pejovic Tanja, Mhawech-Fauceglia Paulette, Rowat Amy C, Drapkin Ronny, Karlan Beth Y, Hazelett Dennis J, Freedman Matthew L, Gayther Simon A, Noushmehr Houtan
Аннотация
Fallopian tube secretory epithelial cells (FTSECs) are likely the main precursor cell type of high-grade serous ovarian cancers (HGSOCs), but these tumors may also arise from ovarian surface epithelial cells (OSECs). We profiled global landscapes of gene expression and active chromatin to characterize molecular similarities between OSECs (n = 114), FTSECs (n = 74), and HGSOCs (n = 394). A one-class machine learning algorithm predicts that most HGSOCs derive from FTSECs, with particularly high FTSEC scores in mesenchymal-type HGSOCs (padj < 8 × 10-4). However, a subset of HGSOCs likely derive from OSECs, particularly HGSOCs of the proliferative type (padj < 2 × 10-4), suggesting a dualistic model for HGSOC origins. Super-enhancer (SE) landscapes were also more similar between FTSECs and HGSOCs than between OSECs and HGSOCs (p < 2.2 × 10-16). The SOX18 transcription factor (TF) coincided with a HGSOC-specific SE, and ectopic overexpression of SOX18 in FTSECs caused epithelial-to-mesenchymal transition, indicating that SOX18 plays a role in establishing the mesenchymal signature of fallopian-derived HGSOCs.