Leveraging the biological features of cell-free DNA to improve cancer detection.

Liquid biopsies, and circulating tumor DNA (ctDNA) in particular, are used to non-invasively detect the presence of cancer cells. ctDNA is commonly detected though the presence of genetic alterations in its sequence. But only a minor fraction of tumor-derived cell-free DNA (cfDNA) fragments exhibits mutations.

The cellular processes occurring in cancer development mark the chromatin, and the mechanisms of release in circulation alter cell-free DNA structure. These signatures can be identified and leveraged with sequencing technologies and liquid biopsy. Epigenomic approaches, based on the examination of cfDNA fragmentation, can detect tumor-derived molecules on a genome-wide scale without pre-existing knowledge of SNVs or SCNAs (Mouliere, et al., 2018, Science Translational Medicine; Mouliere et al., 2018, EMBO Molecular Medicine).

I will present how the recent progress in our understanding of cell-free DNA biology, structure and epigenome are improving the detection of cancer and unlocking new clinical applications.