Clinical application of whole-genome sequencing for precision oncology of solid tumors

Abstract

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. While targeted panel sequencing (TPS) has been a key clinical tool over the past decade, advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) with two primary objectives: 1) assessing actionability for therapeutic options, and 2) providing clarity for clinical questions. Of the 120 various solid cancer patients enrolled, 95 (79%) successfully received genomics reports within a median of 11 working days from sampling to report. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability, and 81% (13/16) to clinical clarity. These benefits encompass selection of informed therapeutics and/or active clinical trials with driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and advocate for its integration into routine clinical practice to provide a complete genomic landscape for tailored cancer management.