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

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. ### Competing Interest Statement R.K., B.B.L.O., E.J., Si.L., J.Y.S., J.-Y.Y., J.P., K.Y., Y.K., W.-C.L., H.P., J.L., B.Y., J.K., J.-Y.K., Sa.L., Y.L., and B.-R.L. are employees of Genome Insight, Inc.. Y.S.J. is a cofounder, board of trustees, shareholder of Genome Insight, Inc. M.K. has received research grants from Genome Insight and Genome and Company. However, this commercial affiliation did not have any role in the data collection and analysis. These co-authors contributed with study design, decision to publish, and preparation of the manuscript. All the other authors declare no conflicts of interest in the authorship or publication of this contribution. ### Funding Statement Genome Insight supported this study in terms of the sequencing provision, and financial support. This research was also supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI23C1589 and HR22C1734 to Minsuk Kwon); the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2022M3A9G101451222 to Young Seok Ju); the new faculty research fund of Ajou University School of Medicine (Minsuk Kwon). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research protocol was approved by the Institutional Review Board (IRB) of Ajou University Hospital (Suwon, Korea; IRB Code: AJOUIRB-SMP-2022-278) and was carried out in alignment with the principles of the Declaration of Helsinki and the stipulations of Good Clinical Practice Guidelines. This prospective, single-center-based genomics trial in the clinical setting (Clinical Research Information Service registration: #KCT0008118) included adult participants with diverse solid cancer types and stages, conducted at Ajou University Hospital (Suwon, South Korea) from September 2022 to April 2023. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors