Unbiased genomic and epigenomic profiling of cell-free plasma DNA for non-invasive cancer screening

Cancer rates are increasing worldwide. A heavier focus on prevention and early detection is required to complement new and improved treatments. We recently optimized a massive parallel sequencing-based analysis pipeline for non-invasive prenatal testing (NIPT) and identified on cellfree DNA samples of 10000 asymptomatic pregnant women 6 genomic representation (GR) profiles reminiscent of cancer-related copy number profiles. These incidental findings triggered us to explore the potential of GR-profiling as an unbiased screening tool for cancer in asymptomatic highrisk individuals. This project aims to technically optimize the sensitivity and specificity of the GR technique, by complementing the existing genome-wide copy number profiling pipeline with methylome profiling. This will extend the cancer detection range towards detection of copy-neutral tumours and will permit tracing the tissue of origin of the circulating tumour DNA. The accuracy of this pipeline for early cancer detection will be evaluated in BRCA mutation carriers, who are at high risk of developing breast or ovarian cancer. Also, we will investigate whether pregnancy-related changes affect the sensitivity of the pipeline to detect aberrations in cell-free tumour DNA. This will ameliorate oncologic examinations during presymptomatic cancer detection in pregnant women.This highly innovative study will reveal whether our genome-wide profiling method is valuable for unbiased non-invasive cancer screening.