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

Henry D Reyes; Eric J Devor; Akshaya Warrier; Andreea M Newtson; Jordan Mattson; Vincent Wagner; Gabrielle N Duncan; Kimberly K Leslie; Jesus Gonzalez-Bosquet

doi:10.1038/s41598-019-54401-w

Back

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

Journal article

Open access

Peer reviewed

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

Henry D Reyes, Eric J Devor, Akshaya Warrier, Andreea M Newtson, Jordan Mattson, Vincent Wagner, Gabrielle N Duncan, Kimberly K Leslie and Jesus Gonzalez-Bosquet

Scientific reports, Vol.9(1), 17996

11/29/2019

DOI: 10.1038/s41598-019-54401-w

PMCID: PMC6884482

PMID: 31784612

Files and links (1)

url

https://doi.org/10.1038/s41598-019-54401-wView

Published (Version of record) Open Access

Abstract

The 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.

Signal Transduction

Case-Control Studies

Cell Line, Tumor

Cystadenocarcinoma, Serous - genetics

Cystadenocarcinoma, Serous - pathology

Cystadenocarcinoma, Serous - surgery

DNA Methylation

Epigenesis, Genetic

Female

Gene Expression Regulation, Neoplastic

Humans

Middle Aged

Neoplasm Grading

Neoplasm Recurrence, Local

Ovarian Neoplasms - genetics

Ovarian Neoplasms - pathology

Ovarian Neoplasms - surgery

Ovariectomy

Ovary - pathology

Ovary - surgery

Retrospective Studies

Treatment Outcome

Details

Title: Subtitle: Differential DNA methylation in high-grade serous ovarian cancer (HGSOC) is associated with tumor behavior
Creators: Henry D Reyes - University at Buffalo, State University of New York
Eric J Devor - Roy J. and Lucille A. Carver College of Medicine
Akshaya Warrier - Roy J. and Lucille A. Carver College of Medicine
Andreea M Newtson - University of Iowa
Jordan Mattson - Roy J. and Lucille A. Carver College of Medicine
Vincent Wagner - Roy J. and Lucille A. Carver College of Medicine
Gabrielle N Duncan - University of Iowa Hospitals and Clinics
Kimberly K Leslie - University of Iowa
Jesus Gonzalez-Bosquet - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Scientific reports, Vol.9(1), 17996
DOI: 10.1038/s41598-019-54401-w
PMID: 31784612
PMCID: PMC6884482
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: P30 CA086862 / NCI NIH HHS R01 CA184101 / NCI NIH HHS
Language: English
Date published: 11/29/2019
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984315564502771

Metrics

13 Record Views

36 Times Cited - Web of Science