Fig. 2

Genomic and transcriptional hallmarks of HRD. Association between HRD status and a the Myriad HRD index score, b contribution of the CX3 copy number signature, c POLQ expression, and d a transcriptional measurement of proliferation/cell cycle arrest capacity. e Enrichment of HRD across breast cancer subtypes. f Enrichment of breast cancer subtypes across HRD status. g Association between HRD status and amplification of MYC. h Enrichment/depletion of somatic nonsynonymous mutations in key cancer genes in HRD and HR-proficient breast cancer samples. A positive log(odds ratio) indicates enrichment in HRD samples. i Positive selection of cancer genes in HR-proficient, all HRD, BRCA1-defective, BRCA2-defective, RAD51C-defective, and HRD BRCA + breast cancer samples. Circle size indicates the strength of positive selection according to the dN/dS ratio. j Comparison of chromosome arm loss and gain events between HRD and HR-proficient breast cancer samples. Positive values indicate enrichment in HRD against HR-proficient samples, whilst the x and y axes indicate enrichment for chromosome arm gains and losses respectively. k Results of differential pathway activity analysis between HRD and HR-proficient breast cancer samples across 14 signalling pathways ordered by the Normalised Enrichment Score (NES). Positive scores indicate pathway enrichment in HRD samples. l Comparison of hypoxia scores in the TCGA-BRCA cohort according to the Buffa transcriptional signature across HRD/BRCA-defect categories, split by ER status. P-values refer to Wilcoxon testing between each group and the HRD-BRCA + group, tested across all samples (black) and ER-negative samples only (red)