MeD-seq, a novel assay for genome-wide DNA methylation profiling in developing predictive biomarkers of gynaecological cancer and endometriosis

To study epigenetic gene regulation with DNA methylation (MeD-seq) in
gynaecological cancers and endometriosis enabling early-stage detection of
gynecological cancers and endometriosis with the MeD-seq method itself or with
a biomarker assay based on the MeD-seq data. The test will eventually be
performed on blood and cervical swabs.
To make this possible, the healthy tissues that will be isolated are crucial to
determine the background signal of DNA methylation and to distinguish
cancer-related DNA methylation changes.
In addition, these healthy tissues are very interesting to use for a much
longer-term goal of mapping the DNA methylation of every cell type in the human
body (DNA methylation atlas).
This DNA methylation atlas will facilitate determination and origination of
cancers whose cell type origin is unknown or unclear (such as e.g. ovarian
cancer in this study) and provide new insights into the pathogenesis of these
cancers and endometriosis and hopefully leads for research into new treatment
methods.

1. To study the possibility to detect gynaecological malignancies and
endometriosis in Pap smears and blood of women with gynaecological cancer or
endometriosis, using MeD-seq and biomarker assays, in order to develop new
reliable screening methods for all different gynaecological malignancies and
endometriosis.
2. To develop a DNA methylation atlas of the healthy female genital cell types
(vulva, vagina, cervix, uterus, tubes and ovaries) using the MeD-seq
technology.

Prospective, longitudinal, observational study with tissue and data collection
of
1. Patients with gynaecological cancer or endometriosis will be asked to
undergo a Pap smear and a blood test for detecting gynaecological malignancies
and endometriosis using the Med-Seq technique (targeted DNA methylation marker
analysis) in Pap smears and blood. Patients do not need to undergo an extra
examination: the Pap smear will only be taken if the patient is in need for an
gynaecological examination for their disease. Blood for research will be taken
during their regular blood examination. We will analyse tissue (redundant for
pathology) post-surgery.
2. Patients without disease but with an indication for surgery because of a
benign disorder. They will be asked whether a small part of their removed
tissues (redundant for pathology) may be used to develop the normal tissue and
cell type DNA methylation atlas.
3. Healthy women consulting the gynaecology department and needing speculum
examination (for example for insertion of an IUD or a Pap smear for population
screening of cervical cancer) will be asked to undergo a Pap smear as a
reference group for 2.

There is no benefit for women participating in this study. They will not
receive a result of the tissue/Pap smear/blood collected. The main disadvantage
is that they have to undergo a Pap smear (a normal diagnostic test that is done
in population screening for cervical cancer) during their gynaecological
examination and donate one tube of blood for cf-DNA extraction. The risk of
taking the Pap smear is negligible and the blood collection will be done during
routine blood collection.