Fig. 5: Clinical utility of WGS in the assessment of therapeutic options: available clinical trials (Category I-2).

a Three cancer cases showing oncogene amplification (CCND1, EGFR) or NRG1 rearrangement, representing genomic targets for clinical trials. b A patient with cholangiocarcinoma harboring ecDNA-mediated FGFR2 hyperamplification, a genomic target for a clinical trial. c The clinical course of a triple-negative breast cancer patient who was identified as a possible candidate for a clinical trial using WGS. Surgically removed tissue from the right axillary lymph node (LN) was subjected to WGS. WGS identified the strong HRD feature and its underlying genetic cause (complete inactivation of somatically acquired BRIP1), which are targets for clinical trials. d Circos plot demonstrating the characteristic HRD features of the patient. Outer to inner: ideogram, point mutations (single base substitutions [SBSs] and short indels) and their variant allele frequencies, distances between adjacent point mutations, major (red line) and minor (blue line) allelic copy number (CN), total segmented CN (black dot) and structural variations (SVs). SBS and SV mutational signatures associated with HRD are shown in pie graphs. e Integrative genome viewer (IGV) snapshot of a somatic SV disrupting the BRCA1 interacting helicase 1 (BRIP1) gene, namely a 21.1-Kbp deletion between BRIP1 intron 14 and BRIP1 intron 6. f A patient with stomach cancer who was identified as a possible candidate for a clinical trial using WGS. WGS identified the strong HRD feature and its underlying genetic cause (a germline BRCA1 pathogenic variant combined with loss of heterozygosity of the locus in the cancer), which are targets for a clinical trial. A Circos plot showing the HRD features mentioned above and two pie graphs showing HRD-associated mutational signatures. g Pathogenic mutations underlying HRD in the patient: we identified germline BRCA1 mutations with loss of heterozygosity in the tumor sample. h Pedigree of the patients. WGS revealed a strong cancer predisposition in the patient’s family. The pathogenic BRCA1 p.L1780P variant was also identified in the younger brother.