10.1371/journal.pone.0196826 Bhuvan Molparia Bhuvan Molparia Glenn Oliveira Glenn Oliveira Jennifer L. Wagner Jennifer L. Wagner Emily G. Spencer Emily G. Spencer Ali Torkamani Ali Torkamani A feasibility study of colorectal cancer diagnosis via circulating tumor DNA derived CNV detection Public Library of Science 2018 CNV detection parent tissue samples cancer progression sample size cfDNA sequencing copy numbers variations stage colorectal cancer pilot stage study 24 CRC samples scale exploration confidence interval DNA sequencing point mutations CNV detection Circulating tumor DNA feasibility study tumor DNA colorectal cancer diagnosis sequencing costs sub-clonal nature ctDNA signal 2018-05-23 17:30:28 Dataset https://plos.figshare.com/articles/dataset/A_feasibility_study_of_colorectal_cancer_diagnosis_via_circulating_tumor_DNA_derived_CNV_detection/6329861 <div><p>Circulating tumor DNA (ctDNA) has shown great promise as a biomarker for early detection of cancer. However, due to the low abundance of ctDNA, especially at early stages, it is hard to detect at high accuracies while keeping sequencing costs low. Here we present a pilot stage study to detect large scale somatic copy numbers variations (CNVs), which contribute more molecules to ctDNA signal compared to point mutations, via cell free DNA sequencing. We show that it is possible to detect somatic CNVs in early stage colorectal cancer (CRC) patients and subsequently discriminate them from normal patients. With 25 normal and 24 CRC samples, we achieve 100% specificity (lower bound confidence interval: 86%) and ~79% sensitivity (95% confidence interval: 63% - 95%,), though the performance should be considered with caution given the limited sample size. We report a lack of concordance between the CNVs detected via cfDNA sequencing and CNVs identified in parent tissue samples. However, recent findings suggest that a lack of concordance is expected for CNVs in CRC because of their sub-clonal nature. Finally, the CNVs we detect very likely contribute to cancer progression as they lie in functionally important regions, and have been shown to be associated with CRC specifically. This study paves the path for a larger scale exploration of the potential of CNV detection for both diagnoses and prognoses of cancer.</p></div>