Clinical application of tumour whole genome sequencing in routine molecular diagnostics for solid cancer patients

Molecular testing is increasingly relevant for enabling precision medicine for cancer patients. Whole genome sequencing (WGS) provides a tumour-agnostic solution for the growing complexity of DNA-based biomarker detection, with promising results demonstrated in various studies. Here, we present real-world data of 888 patients to demonstrate the clinical value of routine use of paired tumour-normal WGS-based diagnostics for solid tumours in a comprehensive cancer center setting. WGS was successful in 89% of cases with a median turnaround time of 6 working days. Potentially actionable biomarkers were identified in 74% of patients, including biomarkers for reimbursed and experimental targeted therapies in 30% and 64% of patients, respectively. Importantly, 38% and 24% of these patients did start biomarker-guided therapy within one year. For cancers of unknown primary (n=123), WGS aided in solving diagnosis or identified reimbursed treatment options in 68% of cases, with 70% starting a tumour type-specific treatment after WGS. Finally, clinically relevant pathogenic germline variants were identified in 6.5% of all patients. Together, routine WGS-based diagnostics outperformed previous study results and had clinical consequences in 42% of all patients tested. WGS thus provides a versatile and future-proof test approach for supporting clinical care for patients with solid cancers.