Assessment of Circulating Copy Number Variant Detection for Cancer Screening

Abstract

Current high-sensitivity cancer screening methods suffer from false positive rates that lead to numerous unnecessary procedures and questionable public health benefit overall. Detection of circulating tumor DNA (ctDNA) has the potential to transform cancer screening. Thus far, nearly all ctDNA studies have focused on detection of tumor-specific point mutations. However, ctDNA point mutation detection methods developed to date lack either the scope or sensitivity necessary to be useful for cancer screening, due to the extremely low (<1%) ctDNA fraction derived from early stage tumors. We suggest that tumor-derived copy number variant (CNV) detection is theoretically a superior means of ctDNA-based cancer screening for many tumor types, given that, relative to point mutations, each individual tumor CNV contributes a much larger number of ctDNA fragments to the overall pool of circulating DNA. Here we perform an in silico assessment of the potential for ctDNA CNV-based cancer screening across many common cancers.