Validation and Implementation of a Somatic-Only Tumor Exome for Routine Clinical Application

Abstract

Next-generation sequencing–based genomic testing is standard of care for tumor workflows. However, its application across different institutions continues to be challenging given the diversity of needs and resource availability among different institutions globally. Moreover, the use of a variety of different panels, including those from a few individual genes to those involving hundreds of genes, results in a relatively skewed distribution of care for patients. It is imperative to obtain a higher level of standardization without having to be restricted to specific kits or requiring repeated validations, which are generally expensive. We show the validation and clinical implementation of the DH-CancerSeq assay, a tumor-only whole-exome–based sequencing assay with integrated informatics, while providing similar input requirements, sensitivity, and specificity to a previously validated targeted gene panel and maintaining similar turnaround times for patient care. Next-generation sequencing–based genomic testing is standard of care for tumor workflows. However, its application across different institutions continues to be challenging given the diversity of needs and resource availability among different institutions globally. Moreover, the use of a variety of different panels, including those from a few individual genes to those involving hundreds of genes, results in a relatively skewed distribution of care for patients. It is imperative to obtain a higher level of standardization without having to be restricted to specific kits or requiring repeated validations, which are generally expensive. We show the validation and clinical implementation of the DH-CancerSeq assay, a tumor-only whole-exome–based sequencing assay with integrated informatics, while providing similar input requirements, sensitivity, and specificity to a previously validated targeted gene panel and maintaining similar turnaround times for patient care. Over the past decade, next-generation sequencing (NGS)–based gene panels have empowered the detection of commonly occurring and actionable somatic variants in solid tumors.1Wakai T. Prasoon P. Hirose Y. Shimada Y. Ichikawa H. Nagahashi M. Next-generation sequencing-based clinical sequencing: toward precision medicine in solid tumors.Int J Clin Oncol. 2019; 24: 115-122Crossref PubMed Scopus (0) Google Scholar, 2Nagahashi M. Shimada Y. Ichikawa H. Kameyama H. Takabe K. Okuda S. Wakai T. Next generation sequencing-based gene panel tests for the management of solid tumors.Cancer Sci. 2019; 110: 6-15Crossref PubMed Scopus (99) Google Scholar, 3Froyen G. Maes B. Clinical validation of targeted solid tumor profiling.Methods Mol Biol. 2019; 1908: 73-87Crossref PubMed Scopus (1) Google Scholar, 4Sunami K. Ichikawa H. Kubo T. Kato M. Fujiwara Y. Shimomura A. et al.Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: a hospital-based study.Cancer Sci. 2019; 110: 1480-1490Crossref PubMed Scopus (239) Google Scholar, 5Mindiola Romero A.E. Tafe L.J. Green D.C. Deharvengt S.J. Winnick K.N. Tsongalis G.J. Baker M.L. Linos K. Levy J.J. Kerr D.A. Utility of retrospective molecular analysis in diagnostically challenging mesenchymal neoplasms.Int J Surg Pathol. 2023; 31: 1473-1484Crossref PubMed Scopus (0) Google Scholar, 6Lindeman N.I. Cagle P.T. Aisner D.L. Arcila M.E. Beasley M.B. Bernicker E.H. Colasacco C. Dacic S. Hirsch F.R. Kerr K. Kwiatkowski D.J. Ladanyi M. Nowak J.A. Sholl L. Temple-Smolkin R. Solomon B. Souter L.H. Thunnissen E. Tsao M.S. Ventura C.B. Wynes M.W. Yatabe Y. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.J Mol Diagn. 2018; 20: 129-159Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar With time, these panels