FIG 3.

Homologous recombination repair defects identified by the Vancouver panel. (A) Bar plot showing allele fractions of four germline and four somatic BRCA2 or ATM truncating mutations identified by the Vancouver panel but not reported by Guardant360. Blue and red bars show mutant allele fraction in the cell-free DNA (cfDNA) sample and matched WBC sample, respectively. (B) Scatter plot showing sequencing coverage log ratios (Vancouver panel) for all 69 autosomal genes in cfDNA of patient 12. Horizontal lines indicate expected log ratios for different copy numbers, given his estimated ctDNA fraction of 72%. Green and orange colors indicate copy number gains and losses, respectively. BRCA2 biallelic loss in chromosome 13 (chr13) is indicated with an arrow. (C) Eleven BRCA2 stop gain reversing somatic alterations detected with the Vancouver panel in cfDNA from patient 17 after treatment with poly (ADP-ribose) polymerase inhibitor olaparib. Deletions are shown as orange rectangles, with length (in base pairs [bp]) shown on the left and number of supporting reads on the right. All deletions overlapping the stop gain mutation are multiple of 3 bp in length and therefore remove the stop gain mutation while avoiding frameshift. Stop gain–reversing base substitutions are shown in the embedded table.