Sensitivity of Genome-wide Analysis of Palindrome Formation

This study seeks to determine the feasibility of a genomic assay for cancer detection by identifying cancer-specific structural aberrations (DNA palindromes) in cell-free DNA (cfDNA) from liquid biopsies. DNA palindromes are inverted DNA repeats that arise from processes that commonly drive genome instability in cancer, such as illegitimate repair of DNA double-strand breaks and breakage-fusion-bridge cycles. Genome-wide Analysis of Palindrome Formation (GAPF) exploits the inherent propensity of denatured DNA palindromes for intra-molecular annealing to enhance tumor signals. To address the sensitivity of GAPF-seq, we serially diluted tumor cell DNA with normal fibroblast DNA and examined the ability of GAPF-seq to call palindromic DNA. Varying relative amounts of input Colo320DM DNA were prepared (100%, 50%, 20%, 10%, and 0%) with the remainder being IMR90 DNA in a total of 1000 ng input DNA.