Fig. 6: Clinical utility of WGS for providing clarity to clinical questions (Category II).

a WGS was supportive in ~81% of the cases conducted for clinical clarity. WGS provided information on the resistance/sensitivity mechanism (II-1), tumor origin (II-2), and evaluation of familial cancer patients (II-3). b A lung adenocarcinoma patient evaluated by WGS to determine the mechanism of resistance to erlotinib treatment. Hyperamplification of the EGFR wild-type allele was found. c In cancer, the MAPK pathway is activated by two mechanisms: (1) EGFR L858R and (2) EGFR-wt amplification. The latter cannot be inhibited by erlotinib. d 2-Deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron-emission tomography-computed tomography (PET-CT) image at the initial presentation of a patient with cancer at an unknown primary site showing a 6.4-cm jejunal mass. A hypermetabolic mass was located in the right adrenal gland and identified as a potential peritoneal carcinomatosis. Additionally, we noted multiple small nodules in both lungs. A computed tomography scan and hematoxylin and eosin image of the right adrenal gland mass are also shown. e Circos plot showing genomic findings from WGS. f Mutational signature analysis of SBSs and IDs. High proportions of SBS4 and ID3 mutational signatures (attributed to tobacco smoking) were noted. g Treatment response to non-small cell lung cancer (NSCLC)-directed chemotherapy: nivolumab plus ipilimumab in combination with paclitaxel plus carboplatin. h A patient with colorectal cancer with a germline APC truncating mutation, suggesting that the cancer was a familial case (familial adenomatous polyposis). i A patient with bilateral breast cancer suspected to have familial cancer given her clinical features and familial history. j, k According to the cancer genome profiling, HRD-associated features were absent, suggesting that bilateral breast cancer was likely sporadic. In line with these observations, no pathogenic germline mutations were found.