A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development

Autor(es):Mostrar menos -

Lawrenson, Kate ^{[1, 2]} ; Fonseca, Marcos A. S. ^[1] ; Liu, Annie Y. ^[1] ; Dezem, Felipe Segato ^[1] ; Lee, Janet M. ^[2] ; Lin, Xianzhi ^[1] ; Corona, Rosario I. ^{[1, 2]} ; Abbasi, Forough ^{[1, 2]} ; Vavra, Kevin C. ^{[1, 2]} ; Dinh, Huy Q. ^[3] ; Gill, Navjot Kaur ^[4] ; Seo, Ji-Heui ^[5] ; Coetzee, Simon ^[2] ; Lin, Yvonne G. ^{[6, 7]} ; Pejovic, Tanja ^{[8, 9, 6]} ; Mhawech-Fauceglia, Paulette ^[10] ; Rowat, Amy C. ^[4] ; Drapkin, Ronny ^[11] ; Karlan, Beth Y. ^[1] ; Hazelett, Dennis J. ^[2] ; Freedman, Matthew L. ^[5] ; Gayther, Simon A. ^[2] ; Noushmehr, Houtan ^{[12, 13]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 - USA

^[2] Cedars Sinai Med Ctr, Dept Biomed Sci, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 - USA

^[3] La Jolla Inst Immunol, Div Inflammat Biol, La Jolla, CA - USA

^[4] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA - USA

^[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 - USA

^[6] Univ Southern Calif, Keck Sch Med, Dept Obstet Gynecol, Div Gynecol Oncol, Los Angeles, CA 90033 - USA

^[7] Genentech Inc, San Francisco, CA - USA

^[8] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 - USA

^[9] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 - USA

^[10] Aurora Diagnost, Austin, TX - USA

^[11] Univ Penn, Dept Obstet & Gynecol, Penn Ovarian Canc Res Ctr, Philadelphia, PA 19104 - USA

^[12] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Sao Paulo, SP - Brazil

^[13] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 - USA

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 29, n. 11, p. 3726+, DEC 10 2019.
• Citações Web of Science: 0

Resumo

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 (p(adj) < 8 x 10(-)(4)). However, a subset of HGSOCs likely derive from OSECs, particularly HGSOCs of the proliferative type (p(adj) < 2 x 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 x 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. (AU)

• Processo FAPESP: 17/08211-1 - Estudo da origem celular do câncer de ovário usando dados genômicos e epigenômicos em larga escala.
• Beneficiário: Marcos Abraão de Souza Fonseca
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico