ABSTRACT
Evaluation of the test performance of the Target enhanced whole-genome sequencing (TE-WGS) assay for comprehensive oncology genomic profiling. The analytical validation of the assay included sensitivity and specificity for single nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs), revealing a revealed a sensitivity of 99.8% for SNVs and 99.2% for indels. The positive predictive value (PPV) was 99.3% SNVs and 98.7% indels. Clinical validation was benchmarked against established orthogonal methods and demonstrated high concordance with reference methods. TE-WGS provides insights beyond targeted panels by comprehensive analysis of key biomarkers and the entire genome encompassing both germline and somatic findings.
Subject(s)
Genomics , INDEL Mutation , Whole Genome Sequencing , Humans , Whole Genome Sequencing/methods , Genomics/methods , Polymorphism, Single Nucleotide , Neoplasms/genetics , Female , Male , Genome, Human , Middle Aged , Sensitivity and Specificity , High-Throughput Nucleotide Sequencing/methods , Aged , Adult , Reproducibility of ResultsABSTRACT
Introduction: Breast cancer exhibits vast genomic diversity, leading to varied clinical manifestations. Integrating molecular subtyping with in-depth genomic profiling is pivotal for informed treatment choices and prognostic insights. Whole-genome clinical analysis provides a holistic view of genome-wide variations, capturing structural changes and affirming tumor suppressor gene loss of heterozygosity. Case Presentation: Here we detail four unique breast cancer cases from Seoul St. Mary's Hospital, highlighting the actionable benefits and clinical value of whole-genome sequencing (WGS). As an all-in-one test, WGS demonstrates significant clinical utility in these cases, including: (1) detecting homologous recombination deficiency with underlying somatic causal variants (case 1), (2) distinguishing double primary cancer from metastasis (case 2), (3) uncovering microsatellite instability (case 3), and (4) identifying rare germline pathogenic variants in TP53 gene (case 4). Our observations underscore the enhanced clinical relevance of WGS-based testing beyond pinpointing a few driver mutations in conventional targeted panel sequencing platforms. Conclusion: With genomic advancements and decreasing sequencing costs, WGS stands out as a transformative tool in oncology, paving the way for personalized treatment plans rooted in individual genetic blueprints.
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.