Methylomic Signatures of High Grade Serous Ovarian Cancer

Published on Dec 8, 2020in Epigenetics4.251
· DOI :10.1080/15592294.2020.1853402
Horacio Cardenas18
Estimated H-index: 18
(NU: Northwestern University),
Fang Fang24
Estimated H-index: 24
(IU: Indiana University)
+ 8 AuthorsKenneth P. Nephew70
Estimated H-index: 70
(IU: Indiana University)
High-grade serous ovarian cancer (HGSOC) harbours aberrant epigenetic features, including DNA methylation. In this study we delineate pathways and networks altered by DNA methylation and associated...
#1Kadi Lõhmussaar (KNAW: Royal Netherlands Academy of Arts and Sciences)H-Index: 4
#2Oded Kopper (KNAW: Royal Netherlands Academy of Arts and Sciences)H-Index: 4
Last. Hans Clevers (KNAW: Royal Netherlands Academy of Arts and Sciences)H-Index: 205
view all 7 authors...
High-grade serous ovarian cancer (HG-SOC)—often referred to as a “silent killer”—is the most lethal gynecological malignancy. The fallopian tube (murine oviduct) and ovarian surface epithelium (OSE) are considered the main candidate tissues of origin of this cancer. However, the relative contribution of each tissue to HG-SOC is not yet clear. Here, we establish organoid-based tumor progression models of HG-SOC from murine oviductal and OSE tissues. We use CRISPR-Cas9 genome editing to introduce ...
18 CitationsSource
#1Amit M. Oza (UHN: University Health Network)H-Index: 21
#2Ursula A. Matulonis (Harvard University)H-Index: 85
Last. Daniela Matei (NU: Northwestern University)H-Index: 59
view all 28 authors...
Purpose: Platinum resistance in ovarian cancer (OC) is associated with epigenetic modifications. Hypomethylating agents (HMAs) have been studied as carboplatin re-sensitizing agents in OC. This randomized phase 2 trial compared guadecitabine, a second generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant OC. Experimental Design: Patients received either G+C (guadecitabine 30 mg/m2 SC once-daily for 5 days and carboplatin)...
24 CitationsSource
#1Shuang ZhangH-Index: 5
#1Shuang ZhangH-Index: 76
Last. Benjamin G. NeelH-Index: 121
view all 6 authors...
The cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8 + FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidl...
50 CitationsSource
#1Linn Gillberg (UCPH: University of Copenhagen)H-Index: 16
#2Andreas Due Ørskov (UCPH: University of Copenhagen)H-Index: 7
Last. Kirsten Grønbæk (UCPH: University of Copenhagen)H-Index: 46
view all 14 authors...
Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis). We conducted a randomized, double-blinded, placebo-c...
21 CitationsSource
#1Yinu Wang (IU: Indiana University)H-Index: 8
#1Yinu Wang (IU: Indiana University)H-Index: 4
Last. Kenneth P. Nephew (IU: Indiana University)H-Index: 70
view all 6 authors...
: In high-grade serous ovarian cancer (OC), chemotherapy eliminates the majority of tumor cells, leaving behind residual tumors enriched in OC stem cells (OCSC). OCSC, defined as aldehyde dehydrogenase-positive (ALDH+), persist and contribute to tumor relapse. Inflammatory cytokine IL-6 is elevated in residual tumors after platinum treatment, and we hypothesized that IL-6 plays a critical role in platinum-induced OCSC enrichment. We demonstrate that IL-6 regulates stemness features of OCSC drive...
45 CitationsSource
#1Steven C. Eastlack (LSU Health Sciences Center New Orleans)H-Index: 5
#2Shengli Dong (LSU Health Sciences Center New Orleans)H-Index: 18
Last. Suresh K. Alahari (LSU Health Sciences Center New Orleans)H-Index: 32
view all 4 authors...
The disruption of normal gene regulation due to microRNA dysfunction is a common event in cancer pathogenesis. MicroRNA-27b is an example of an oncogenic miRNA, and it is frequently upregulated in breast cancer. MicroRNAs have been found to deregulate tumor metabolism, which typically manifests as heightened cellular glucose uptake in consort with increased flux through glycolysis, followed by the preferential conversion of glycolytic pyruvate into lactate (a phenomenon known as the Warburg Effe...
30 CitationsSource
#1Lindsey A. Torre (ACS: American Cancer Society)H-Index: 16
#2Britton Trabert (NIH: National Institutes of Health)H-Index: 38
Last. Rebecca L. Siegel (ACS: American Cancer Society)H-Index: 67
view all 9 authors...
: In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined f...
940 CitationsSource
#1Daniela Matei (NU: Northwestern University)H-Index: 59
#2Sharad A. GhamandeH-Index: 17
Last. Gini F. Fleming (U of C: University of Chicago)H-Index: 73
view all 14 authors...
Purpose: Epigenetic changes are implicated in acquired resistance to platinum. Guadecitabine is a next-generation hypomethylating agent (HMA). Here, we report the clinical results, along with pharmacokinetic (PK) and pharmacodynamic analyses of the phase I study of guadecitabine and carboplatin in patients with recurrent, platinum-resistant high-grade serous ovarian cancer, primary peritoneal carcinoma (PPC), or fallopian tube cancer (FTC). Experimental Design: Guadecitabine was administered onc...
35 CitationsSource
#1Yonghong ZhangH-Index: 15
#2Sophie Petropoulos (McGill University)H-Index: 18
Last. Moshe Szyf (McGill University)H-Index: 75
view all 9 authors...
Background The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support.
33 CitationsSource
#1Dapeng Hao (UM: University of Macau)H-Index: 6
#2Jingjing Li (UM: University of Macau)H-Index: 7
Last. Lijun Di (UM: University of Macau)H-Index: 17
view all 7 authors...
Purpose: The relative importance of fallopian tube (FT) compared to ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. Experimental Design: A collection of transcriptome data of 80 FTs, 89 OSEs and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and ...
25 CitationsSource
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