Fig. 4.

Cell-free DNA fragmentation patterns in PDAC. (A) Cell free DNA molecules display a characteristic modal fragment size ∼167bp; 147bp of DNA are wrapped around a nucleosome with a 10bp periodicity corresponding to the helical pitch of DNA on the nucleosome core, and 20bp of linker DNA constitute the remainder of cfDNA fragments. Although DNA within the nucleosome core is protected from endonuclease activity, regions of linker DNA remain vulnerable to digestion, leading to small variations in this modal fragment size between cfDNA samples, which can be explained by varying linker lengths. (B) In contrast, ctDNA fragmentation profiles have been shown to be more variable than non-tumour cfDNA, as tumour cell necrosis and mechanisms of active release can also contribute to overall levels of tumour-derived ctDNA fragments in blood. Mutant ctDNA fragments in PDAC have been detected at both short (≤150bp) and long (>150bp) fragment sizes, with varying degrees of enrichment observed within each size fraction. (C) Patterns of cfDNA and ctDNA cleavage are evidenced in fragment size distribution profiles, as shown in (B).