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Clinical Application of Whole-Genome Sequencing of Solid Tumors for Precision Oncology

EXPERIMENTAL AND MOLECULAR MEDICINE(2024)

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Abstract
Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but 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) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. 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) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of 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 suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management. Personalized medicine customizes cancer treatment to each patient, using molecular profiling of tumors to find specific genetic changes that can guide treatment. Despite progress, the practical use of whole-genome sequencing in clinical settings is still not fully explored. This study examines the use of WGS for cancer patients, aiming to make it a regular part of care. The study involved 120 participants with various solid tumors, using the CancerVisionTM for sequencing. Researchers conclude that WGS is a valuable tool in precision oncology, offering insights that can significantly impact treatment strategies. The study marks progress in integration of genomic medicine into clinical practice, showcasing the feasibility and benefits of WGS in a real-world hospital setting. Future research may further establish WGS as a standard part of cancer care, potentially changing how we approach treatment for different tumor types. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
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Key words
Cancer Genomics,Precision Medicine,Intratumor Heterogeneity
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