While this signature was not robustly detected in the cell line sequences even if they contained BRCA1,2 mutation and confirmed HRd (Fig. 5d), most probably because the signature is flat and cannot be reliably identified from exome data, analysis of published osteosarcoma whole genome data7 confirmed RB1 defects are not significantly associated with HRd exposure using this parameter (Supplementary Fig. 5a). This evidence concerns the gene RB1 and osteosarcoma.