Abstract 3154: Cell-free circulating tumor DNA methylation in high-grade serous ovarian cancer

2016 ◽  
Author(s):  
Kayleigh R. Davis ◽  
Kirsty J. Flower ◽  
Jane V. Borley ◽  
Charlotte SM Wilhelm-Benartzi ◽  
Robert Brown
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Tumor Dna

Abstract 4587:ESR1methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer

2018 ◽  
Author(s):  
Lydia Giannopoulou ◽  
Sofia Mastoraki ◽  
Areti Strati ◽  
Issam Chebouti ◽  
Kitty Pavlakis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Tumor Dna

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer

2018 ◽  
Vol 150 (2) ◽  
pp. 355-360 ◽  
Author(s):  
Lydia Giannopoulou ◽  
Sophia Mastoraki ◽  
Paul Buderath ◽  
Areti Strati ◽  
Kitty Pavlakis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Circulating Tumor Dna ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Tumor Dna

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

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Pietro Lo Riso ◽  
Carlo Emanuele Villa ◽  
Gilles Gasparoni ◽  
Andrea Vingiani ◽  
Raffaele Luongo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Differentially Expressed ◽  
Prognostic Impact ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Tumor Subtypes ◽  
Transcriptional Alterations ◽  
Bona Fide ◽  
Tissue Of Origin

Abstract Background High-grade serous ovarian cancer (HGSOC) is a major unmet need in oncology. The remaining uncertainty on its originating tissue has hampered the discovery of molecular oncogenic pathways and the development of effective therapies. Methods We used an approach based on the retention in tumors of a DNA methylation trace (OriPrint) that distinguishes the two putative tissues of origin of HGSOC, the fimbrial (FI) and ovarian surface epithelia (OSE), to stratify HGSOC by several clustering methods, both linear and non-linear. The identified tumor subtypes (FI-like and OSE-like HGSOC) were investigated at the RNAseq level to stratify an in-house cohort of macrodissected HGSOC FFPE samples to derive overall and disease-free survival and identify specific transcriptional alterations of the two tumor subtypes, both by classical differential expression and weighted correlation network analysis. We translated our strategy to published datasets and verified the co-occurrence of previously described molecular classification of HGSOC. We performed cytokine analysis coupled to immune phenotyping to verify alterations in the immune compartment associated with HGSOC. We identified genes that are both differentially expressed and methylated in the two tumor subtypes, concentrating on PAX8 as a bona fide marker of FI-like HGSOC. Results We show that: - OriPrint is a robust DNA methylation tracer that exposes the tissue of origin of HGSOC. - The tissue of origin of HGSOC is the main determinant of DNA methylation variance in HGSOC. - The tissue of origin is a prognostic factor for HGSOC patients. - FI-like and OSE-like HGSOC are endowed with specific transcriptional alterations that impact patients’ prognosis. - OSE-like tumors present a more invasive and immunomodulatory phenotype, compatible with its worse prognostic impact. - Among genes that are differentially expressed and regulated in FI-like and OSE-like HGSOC, PAX8 is a bona fide marker of FI-like tumors. Conclusions Through an integrated approach, our work demonstrates that both FI and OSE are possible origins for human HGSOC, whose derived subtypes are both molecularly and clinically distinct. These results will help define a new roadmap towards rational, subtype-specific therapeutic inroads and improved patients’ care.

Abstract 5318: High-grade serous ovarian cancer DNA methylation and survival in African-American women

2018 ◽  
Author(s):  
Lucas A. Salas ◽  
Lauren C. Peres ◽  
Sarah E. Abbott ◽  
Casey S. Greene ◽  
Jeffrey R. Marks ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
African American ◽  
African American Women ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
American Women

scholarly journals Differential DNA methylation in high-grade serous ovarian cancer (HGSOC) is associated with tumor behavior

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Henry D. Reyes ◽  
Eric J. Devor ◽  
Akshaya Warrier ◽  
Andreea M. Newtson ◽  
Jordan Mattson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Dna Methylation ◽  
Surgical Outcomes ◽  
Methylation Status ◽  
Hippo Signaling ◽  
Gene Promoters ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Differentially Methylated Genes

AbstractThe epigenome offers an additional facet of cancer that can help categorize patients into those at risk of disease, recurrence, or treatment failure. We conducted a retrospective, nested, case-control study of advanced and recurrent high-grade serous ovarian cancer (HGSOC) patients in which we assessed epigenome-wide association using Illumina methylationEPIC arrays to characterize DNA methylation status and RNAseq to evaluate gene expression. Comparing HGSOC tumors with normal fallopian tube tissues we observe global hypomethylation but with skewing towards hypermethylation when interrogating gene promoters. In total, 5,852 gene interrogating probes revealed significantly different methylation. Within HGSOC, 57 probes highlighting 17 genes displayed significant differential DNA methylation between primary and recurrent disease. Between optimal vs suboptimal surgical outcomes 99 probes displayed significantly different methylation but only 29 genes showed an inverse correlation between methylation status and gene expression. Overall, differentially methylated genes point to several pathways including RAS as well as hippo signaling in normal vs primary HGSOC; valine, leucine, and isoleucine degradation and endocytosis in primary vs recurrent HGSOC; and pathways containing immune driver genes in optimal vs suboptimal surgical outcomes. Thus, differential DNA methylation identified numerous genes that could serve as potential biomarkers and/or therapeutic targets in HGSOC.

scholarly journals The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Martin Widschwendter ◽  
Michal Zikan ◽  
Benjamin Wahl ◽  
Harri Lempiäinen ◽  
Tobias Paprotka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Circulating Tumor Dna ◽  
Methylation Analysis ◽  
Dna Methylation Analysis ◽  
Tumor Dna

scholarly journals Prognostic Significance of SLFN11 Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 4
Author(s):  
Victoria Tserpeli ◽  
Dimitra Stergiopoulou ◽  
Dora Londra ◽  
Lydia Giannopoulou ◽  
Paul Buderath ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Liquid Biopsy ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Gene Promoters ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Platinum Based Chemotherapy

Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment. Methods: In the present study, we examined the methylation status of six gene promoters (BRCA1, CST6, MGMT, RASSF10, SLFN11 and USP44) in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC. Results: We report for the first time that the DNA methylation of SLFN11 in plasma cfDNA was significantly correlated with worse PFS (p = 0.045) in advanced stage HGSOC. Conclusions: Our results strongly indicate that SLFN11 epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of SLFN11 promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer.

Sign in / Sign up

Export Citation Format

Share Document