66 Chapter 3 EXECUTIVE SUMMARY A systematic review of the literature on DNA methylation markers for endometrial cancer detection • A total of nine studies that investigated DNA methylation markers for the minimally invasive detection of endometrial cancer (EC) were included, resulting in 15 potential DNA methylation markers with area under the curve values ranging from 0.80 to 0.96. Promising DNA methylation marker selection • Comparability of studies was hampered due to differences in population selection, characteristics of case and control groups, sample type, sample preparation, DNA methylation detection techniques and the cut-off values used to handle DNA methylation levels. • Despite the above-mentioned differences among studies, the individual genes ADCYAP1, ASCL2, BHLHE22, CDH13, CDO1, CELF4, GALR1, HAND2, HS3ST2, HTR1B, MAGI2, MME, POU4F3, RASSF1 and ZNF662 were considered promising for EC detection according to their area under the curve value of ≥ 0.80 for distinguishing benign endometrium from EC. Conclusion • We selected 15 promising DNA methylation markers for the minimally invasive detection of EC using cell specimens. • DNA methylation markers would be clinically relevant for the detection of EC in women presenting with postmenopausal bleeding, during cancer screening programs and potentially in women with Lynch syndrome. Validation in larger, prospective and unbiased cohorts is warranted to determine their true diagnostic accuracy. • The performance of selected methylation markers with potential clinical value may be improved by combining DNA methylation markers with additional (epi)genetic markers and using alternative sources of DNA. Financial & competing interests disclosure This work was supported by Hanarth Foundation and Weijerhorst Foundation, who provided financial support for the conduct of the research and had no role in conducting the research and preparation of the manuscript. RDM Steenbergen has a minority share in Self-screen B.V., a spin-off company of Amsterdam UMC, location VUmc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
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