scholarly journals Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

2018 ◽  
Author(s):  
Kate Lawrenson ◽  
Marcos A.S. Fonseca ◽  
Felipe Segato ◽  
Janet M. Lee ◽  
Rosario I. Corona ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Tumor Development ◽  
Molecular Profiling ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Ovarian Cancers ◽  
Integrative Analyses ◽  
Ovarian Surface Epithelial

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.

scholarly journals Odd-skipped related 2 (OSR2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Cell Fate ◽  
Microarray Data ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2,3). We previously identified forkhead box L2 (4), (FOXL2) as among the genes whose expression was most different in HGSC ovarian tumors when compared to the ovary. Here, we find that potential FOXL2 transcriptional target (5,6) odd-skipped related gene OSR2 (7) is differentially expressed in high-grade serous ovarian cancer, and could be observed in independent tumor microarray data (2,3). These data reveal perturbed expression of a target gene of a key transcription factor and specifier of ovarian cell fate in high-grade serous ovarian cancers.

scholarly journals Metformin induces distinct bioenergetic and metabolic profiles in sensitive versus resistant high grade serous ovarian cancer and normal fallopian tube secretory epithelial cells

Oncotarget ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 4044-4060 ◽  
Author(s):  
Melissa Hodeib ◽  
Martin P. Ogrodzinski ◽  
Laurent Vergnes ◽  
Karen Reue ◽  
Beth Y. Karlan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Fallopian Tube ◽  
Metabolic Profiles ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 262 ◽  
Author(s):  
Laura Hardy ◽  
Amrita Salvi ◽  
Joanna Burdette
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Cancer Progression ◽  
Drug Targets ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Pax8 Expression

High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

Distinct T cell receptor diversity and integrative analyses of clinically defined high-grade serous ovarian cancer

2021 ◽  
Vol 162 ◽  
pp. S138
Author(s):  
Sanghoon Lee ◽  
Li Zhao ◽  
Latasha Little ◽  
Shannon Westin ◽  
Amir Jazaeri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Integrative Analyses

scholarly journals Progesterone Prevents High-Grade Serous Ovarian Cancer by Inducing Necroptosis of p53-Defective Fallopian Tube Epithelial Cells

Cell Reports ◽  
2017 ◽  
Vol 18 (11) ◽  
pp. 2557-2565 ◽  
Author(s):  
Na-Yiyuan Wu ◽  
Hsuan-Shun Huang ◽  
Tung Hui Chao ◽  
Hsien Ming Chou ◽  
Chao Fang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Cells ◽  
Fallopian Tube ◽  
High Grade ◽  
Serous Ovarian Cancer

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

Cell Reports ◽  
2019 ◽  
Vol 29 (11) ◽  
pp. 3726-3735.e4 ◽  
Author(s):  
Kate Lawrenson ◽  
Marcos A.S. Fonseca ◽  
Annie Y. Liu ◽  
Felipe Segato Dezem ◽  
Janet M. Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transcription Factor ◽  
Tumor Development ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals Microscopic Peritoneal Residual Disease after Complete Macroscopic Cytoreductive Surgery for Advanced High Grade Serous Ovarian Cancer

2020 ◽  
Vol 10 (1) ◽  
pp. 41
Author(s):  
Henri Azaïs ◽  
Anne-Sophie Vignion-Dewalle ◽  
Marine Carrier ◽  
Jeremy Augustin ◽  
Elisabeth Da Maïa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Systemic Chemotherapy ◽  
Residual Disease ◽  
Peritoneal Metastases ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Conventional Surgery ◽  
Ovarian Cancers ◽  
A Prospective Study

Background: Epithelial ovarian cancers (EOC) are usually diagnosed at an advanced stage and managed by complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy. Peritoneal recurrence occurs in 60% of patients and may be due to microscopic peritoneal metastases (mPM) which are neither eradicated by surgery nor controlled by systemic chemotherapy. The aim of this study was to assess and quantify the prevalence of residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). Methods: A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. A mathematical model was designed to determine the probability of presenting at least one mPM after CRS. Results: 26 patients were included and 26.9% presented mPM. There were no differences in characteristics between patients with or without identified mPM. After mathematical analysis, the probability that mPM remained after complete macroscopic CRS in patients with EOC was 98.14%. Conclusion: Microscopic PM is systematically present after complete macroscopic CRS for EOC and could be a relevant therapeutic target. Adjuvant locoregional strategies to conventional surgery may improve survival by achieving microscopic CRS.

scholarly journals A cell-of-origin epigenetic tracer reveals clinically distinct subtypes of high grade serous ovarian cancer

2018 ◽  
Author(s):  
Pietro Lo Riso ◽  
Carlo Emanuele Villa ◽  
Gilles Gasparoni ◽  
Raffaele Luongo ◽  
Anna Manfredi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Unmet Need ◽  
Prognostic Impact ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Oncogenic Pathways ◽  
Transcriptomic Signature ◽  
A Cell ◽  
Disease Subtypes

AbstractHigh grade serous ovarian cancer (HGSOC) is a major unmet need in oncology. The persistent uncertainty on its originating tissue has contributed to hamper the discovery of oncogenic pathways and effective therapies. Here we define the DNA methylation print that distinguishes the human fimbrial (FI) and ovarian surface epithelia (OSE) and develop a robust epigenetic cell-of-origin tracer that stratifies HGSOC in FI-and OSE-originated tumors across all available cohorts. We translate this origin-based stratification into a clinically actionable transcriptomic signature, demonstrating its prognostic impact on patients’ survival and identifying novel network level dysregulations specific for the two disease subtypes.

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