A large cohort study at the Netherlands Cancer Institute found that whole-genome sequencing (WGS) identified potentially actionable biomarkers in 73% of cases.
A study published in Nature Medicine on March 20, 2026, analyzed tumor samples from 935 patients with solid tumors. The research demonstrated that positioning WGS earlier in the diagnostic pathway may improve outcomes, as it is currently often used as a last-resort test.
Key Findings
WGS generated diagnostic reports in 89% of cases (793 of 888 samples) with a median turnaround time of six working days. Failures in 11% of samples were mainly due to insufficient tumor content or DNA quality.
Among 723 patients with linked clinical data, WGS identified potentially actionable biomarkers in 73% of cases. Of those with actionable biomarkers:
- 27% were linked to funded standard-of-care treatments
- 63% suggested potential eligibility for newer or investigational therapies
Survival Outcomes
Patients receiving biomarker-informed treatment after WGS had a 31% longer median overall survival (405 days vs. 309 days; HR 0.78).
The survival benefit was concentrated in treatment-naive patients receiving first-line biomarker-informed therapy:
- Median survival not reached after four years for first-line biomarker-guided therapy
- 427 days (HR 0.52) for non-biomarker-guided therapy
- 214 days (HR 0.37) for no systemic therapy
In pre-treated patients, biomarker-informed therapy did not show a clear survival advantage.
Additional Clinical Insights
Among cancers of unknown primary (CUP), 63% received a definitive tumor-type diagnosis, 73% had at least one actionable biomarker, and 68% of those with treatment data received systemic therapy.
Pathogenic germline variants were detected in 6.5% of patients, about half not previously detected. This highlights WGS's potential to uncover hereditary cancer risks that might otherwise go unnoticed.
Comparison with Standard Panels
Compared to a typical 50-gene NGS panel (actionable in 49%) and a 523-gene panel (70%), WGS identified additional actionable findings in 8% of cases.
Important Caveats
- Not all patients received biomarker-informed therapy
- The advantage over non-biomarker-guided systemic therapy was not statistically significant
- The study notes that WGS is currently often used as a last-resort test, suggesting earlier use may yield better results