Journal Article

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

Unmehopa, Unga, van der Hoeven, Jacobus J. M., Schipper, Luuk J., van Snellenberg, Hans, van den Burg, Kay, Hogervorst, Frans B. L., van der Kolk, Lizet E., Roepman, Paul, Riethorst, Immy, Schout, Daoin, Boelens, Mirjam C., van Linder, Berit M. H., Monkhorst, Kim, van Beek, Daphne, Voest, Emile E., Samsom, Kris G., de Bruijn, Ewart, Schoenmaker, Lieke, de Langen, Adrianus J., Buffart, Tineke E., Klompenhouwer, Elisabeth G., Meijer, Gerrit A., van Deventer, Kelly, Rosenberg, Efraim H., Cuppen, Edwin, Bosch, Linda J. W., Lalezari, Ferry, Koster, Roelof, van den Berg, José G.

2024

Overview

Two decades after the genomics revolution, oncology is rapidly transforming into a genome-driven discipline, yet routine cancer diagnostics is still mainly microscopy based, except for tumor type-specific predictive molecular tests. Pathology laboratories struggle to quickly validate and adopt biomarkers identified by genomics studies of new targeted therapies. Consequently, clinical implementation of newly approved biomarkers suffers substantial delays, leading to unequal patient access to these therapies. Whole-genome sequencing (WGS) can successfully address these challenges by providing a stable molecular diagnostic platform that allows detection of a multitude of genomic alterations in a single cost-efficient assay and facilitating rapid implementation, as well as by the development of new genomic biomarkers. Recently, the Whole-genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE) study demonstrated that WGS is a feasible and clinically valid technique in routine clinical practice with a turnaround time of 11 workdays. As a result, WGS was successfully implemented at the Netherlands Cancer Institute as part of routine diagnostics in January 2021. The success of implementing WGS has relied on adhering to a comprehensive protocol including recording patient information, sample collection, shipment and storage logistics, sequencing data interpretation and reporting, integration into clinical decision-making and data usage. This protocol describes the use of fresh-frozen samples that are necessary for WGS but can be challenging to implement in pathology laboratories accustomed to using formalin-fixed paraffin-embedded samples. In addition, the protocol outlines key considerations to guide uptake of WGS in routine clinical care in hospitals worldwide. Key points Whole-genome sequencing analysis detects DNA changes in the whole cancer genome, allowing identification of new, clinically relevant biomarkers, and opening the doors to a new era of tumor diagnostic and personalized cancer medicine. The protocol provides a detailed workflow covering patient selection, sample handling, and interpretation and reporting of the results, facilitating implementation of whole-genome sequencing analysis in routine oncology clinical practice. This protocol presents a comprehensive workflow for the implementation of whole-genome sequencing in routine tumor diagnostics, exemplified by the pipeline used in the Netherlands Cancer Institute.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337 / 631/67/69 / 692/4017 / 692/4028/67/68 / Analytical Chemistry / Biological Techniques / Biomarkers / Biomedical and Life Sciences / Cancer / Clinical medicine / Computational Biology/Bioinformatics / Data interpretation / Decision making / Diagnostic systems / DNA sequencing / Genomes / Genomics / Humans / Laboratories / Life Sciences / Microarrays / Neoplasms - diagnosis / Neoplasms - genetics / Neoplasms - pathology / Oncology / Organic Chemistry / Pathology / Patients / Protocol / Tumors / Whole genome sequencing / Whole Genome Sequencing - methods / Workflow