Fig. 2

HRD-high tumors co-occurring with TP53 mutations are associated with worse PFS. A Unsupervised clustering of genomic features. HRD cluster: classification of tumors harboring higher (HRD-H) or lower (HRD-L) level of HRD genomic scar features. S2 and S13 (APOBEC): mutation signatures 2 and 13 linked to APOBEC enzyme activity. S3 (HRD): mutation signature linked to homologous recombination deficiency. CYT score: cytolytic activity score calculated from mRNA expression levels of GZMA and PRF1. CIN, chromosome instability; TAI, telomeraic allelic imbalance; LOH, loss-of-heterozygosity; LST, large-scale transitions. Subtype: PAM50 subtype classification. B HRD-H cluster significantly enriched in BRCA1/2 mutations (Fisher’s exact test: p = 92.e−05). C HRD-H cluster significantly enriched in luminal B subtype (Fisher’s exact test: p = 0.0108436). D, E HRD-H cluster significantly enriched in HRD index (D) and mutation signature S3 (E) in the overall cohort and within luminal A and luminal B subtypes (Wilcoxon). F HRD-high cluster significantly associated with shorter PFS. G Kaplan-Meier plots comparing PFS between the four groups of baseline samples with different mutation statuses for TP53 and BRCA1/2. HR and 95% CI shown in parentheses. BRCA.mut+TP53.mut: co-occurring BRCA1/2 pathogenic mutation and TP53 somatic mutations. H Kaplan-Meier plots comparing PFS between the four groups of baseline samples with different statuses of HRD cluster and TP53 mutation. WT: TP53 wild type and HRD-Low. TP53.mut: TP53 mutation and HRD-Low. HRD-H: HRD-High and TP53 wild type. HRD-H+TP53.mut: TP53 somatic mutation and HRD-High