Optimized whole-genome sequencing workflow for tumor diagnostics in routine pathology practice

Area of Science:

• Genomic Medicine
• Oncology Diagnostics
• Translational Research

Background:

• Current cancer diagnostics rely heavily on microscopy, delaying the integration of genomic biomarkers into clinical practice.
• Pathology labs face challenges in validating and adopting new biomarkers identified through genomics studies.
• This delay hinders timely patient access to novel targeted therapies.

Purpose of the Study:

• To evaluate the feasibility and clinical validity of whole-genome sequencing (WGS) as a routine diagnostic tool in oncology.
• To demonstrate the potential of WGS to accelerate the implementation of genomic biomarkers and targeted therapies.
• To provide a comprehensive protocol for the successful integration of WGS into standard pathology workflows.

Main Methods:

• The Whole-genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE) study assessed WGS in routine clinical practice.
• A comprehensive protocol was developed, covering sample handling, data interpretation, reporting, and clinical integration.
• The study utilized fresh-frozen samples, a key consideration for WGS implementation.

Main Results:

• WGS proved to be a feasible and clinically valid diagnostic technique with a rapid turnaround time of 11 workdays.
• Successful implementation of WGS into routine diagnostics was achieved at the Netherlands Cancer Institute in January 2021.
• The established protocol facilitated the integration of WGS into clinical decision-making.

Conclusions:

• Whole-genome sequencing (WGS) provides a robust and efficient platform for comprehensive genomic profiling in cancer patients.
• Implementing WGS can significantly reduce diagnostic delays and improve patient access to precision oncology treatments.
• The outlined protocol offers a roadmap for pathology laboratories worldwide to adopt WGS in routine clinical care.