Detecting prostate cancer with circulating tumour DNA methylation. - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Radoslaw Lach ^1,2 Gahee Park ^1,2 Sara Pita ^1,2 Anne Babbage ^1,2 Wing Kit Leung ³ Jelena Belic ^1,2 Anne George ¹ ICGC Working Group UK ¹ Anne Warren ⁴ Vincent Gnanapragasam ⁵ Andy Lynch ³ Charlie Massie ^1,2

¹Department of Oncology, University of Cambridge, UK
²Early Detection Programme, CRUK Cambridge Cancer Centre, UK
³Cancer Research UK Cambridge Institute, University of Cambridge, UK
⁴Department of Pathology, Addenbrooke’s Hospital, UK
⁵Department of Surgery, University of Cambridge, UK

Prostate cancer is the fourth most common cancer worldwide with 1.3 million new cases in 2018. Current non-invasive diagnostics show low specificity while invasive alternatives may lead to complications. Circulating tumour DNA (ctDNA) is a promising non-invasive target to improve the specificity of prostate tumour diagnosis.

Alterations in DNA methylation are common characteristic of many cancers, including prostate cancer. These alterations were previously demonstrated to be useful in clinical diagnosis.

Using sequence capture followed by bisulfite conversion and second-generation sequencing, we identified a set of differentially methylated regions (DMRs) in tumour biopsies of 26 prostate cancer patients. We combined these data with DMRs found in over three hundred prostate tumours using array technology (TCGA-PRAD). We excluded from further analysis DMRs showing similarity in methylation patterns between tumours and cfDNA of healthy controls. We optimized methods for analysis of cfDNA methylation and modelled bisulfite over- and underconversion rates. We will present preliminary results of tumour DMR analysis in blood of prostate cancer patients and a first approximation of its diagnostic potential.