Figure 5.

Relationship between DDR deficiency, replication stress, and therapeutic response in PDCLs of PC. PDCLs are ranked based on a novel transcriptomic signature of replication stress (y-axis) and a composite genomic readout of DDR deficiency (x-axis). DDR deficiency is a hierarchical score that incorporates the COSMIC BRCA mutational signature (signature 3), the number of structural variants distributed across the genome, and the GPOL HRD test associated with BRCA deficiency. Relative HRDetect score is indicated by colored scale. The combination of high/low states of each characteristic results in 4 groups. Squamous subtype PDCLs (blue squares) are associated with high replication stress (P = .007, chi-square test). PDCLs tested are identified and encircled in blue. DDR deficiency and the replication stress signature predicted differential therapeutic response.