The DNA methylome of cervical cells can predict the presence of ovarian cancer

James E Barrett; Allison Jones; Iona Evans; Daniel Reisel; Chiara Herzog; Kantaraja Chindera; Mark Kristiansen; Olivia C Leavy; Ranjit Manchanda; Line Bjørge; Michal Zikan; David Cibula; Martin Widschwendter

doi:10.1038/s41467-021-26615-y

The DNA methylome of cervical cells can predict the presence of ovarian cancer

Nat Commun. 2022 Feb 1;13(1):448. doi: 10.1038/s41467-021-26615-y.

Authors

James E Barrett^{1

2

3}, Allison Jones³, Iona Evans³, Daniel Reisel³, Chiara Herzog^{1

2}, Kantaraja Chindera³, Mark Kristiansen⁴, Olivia C Leavy^{5

6}, Ranjit Manchanda^{7

8

9}, Line Bjørge^{10

11}, Michal Zikan^{12

13}, David Cibula¹³, Martin Widschwendter^{14

15

16

17}

Affiliations

¹ European Translational Oncology Prevention and Screening (EUTOPS) Institute, 6060, Hall in Tirol, Austria.
² Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria.
³ Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, 74 Huntley Street, London, WC1E 6AU, UK.
⁴ UCL Genomics, Zayed Centre for Research into Rare Disease in Children, University College London, London, WC1N 1DZ, UK.
⁵ Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
⁶ Department of Non-communicable Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
⁷ Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, E1 1BB, UK.
⁸ Centre for Prevention, Detection & Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, EC1M 6BQ, UK.
⁹ Department of Health Services Research, The London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
¹⁰ Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway.
¹¹ Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
¹² Hospital Na Bulovce, Prague, Czech Republic.
¹³ Department of Obstetrics and Gynecology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁴ European Translational Oncology Prevention and Screening (EUTOPS) Institute, 6060, Hall in Tirol, Austria. martin.widschwendter@uibk.ac.at.
¹⁵ Research Institute for Biomedical Aging Research, Universität Innsbruck, 6020, Innsbruck, Austria. martin.widschwendter@uibk.ac.at.
¹⁶ Department of Women's Cancer, UCL EGA Institute for Women's Health, University College London, 74 Huntley Street, London, WC1E 6AU, UK. martin.widschwendter@uibk.ac.at.
¹⁷ Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. martin.widschwendter@uibk.ac.at.

Abstract

The vast majority of epithelial ovarian cancer arises from tissues that are embryologically derived from the Müllerian Duct. Here, we demonstrate that a DNA methylation signature in easy-to-access Müllerian Duct-derived cervical cells from women with and without ovarian cancer (i.e. referred to as the Women's risk IDentification for Ovarian Cancer index or WID-OC-index) is capable of identifying women with an ovarian cancer in the absence of tumour DNA with an AUC of 0.76 and women with an endometrial cancer with an AUC of 0.81. This and the observation that the cervical cell WID-OC-index mimics the epigenetic program of those cells at risk of becoming cancerous in BRCA1/2 germline mutation carriers (i.e. mammary epithelium, fallopian tube fimbriae, prostate) further suggest that the epigenetic misprogramming of cervical cells is an indicator for cancer predisposition. This concept has the potential to advance the field of risk-stratified cancer screening and prevention.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

BRCA1 Protein / genetics
BRCA1 Protein / metabolism
BRCA2 Protein / genetics
BRCA2 Protein / metabolism
Cervix Uteri / cytology
Cervix Uteri / metabolism*
DNA Methylation*
Epigenome
Epithelium / metabolism*
Female
Genetic Predisposition to Disease
Humans
Ovarian Neoplasms / genetics*
Ovarian Neoplasms / metabolism

Substances

BRCA1 Protein
BRCA2 Protein