Analytic validation and clinical utilization of the comprehensive genomic profiling test, GEM ExTra®

Abstract

// Tracey White 1 , * , Szabolcs Szelinger 1 , * , Janine LoBello 1 , Amy King 1 , Jessica Aldrich 1 , Nathan Garinger 1 , Matthew Halbert 1 , Ryan F. Richholt 1 , Stephen D. Mastrian 1 , Cody Babb 1 , Audrey A. Ozols 1 , Laurie J. Goodman 1 , Gargi D. Basu 1 and Thomas Royce 1 1 Ashion Analytics, LLC, Phoenix, Arizona 85004, USA * These authors contributed equally to this work Correspondence to: Thomas Royce, email: TRoyce@ashion.com Keywords: comprehensive genomic profiling; whole exome sequencing; RNA sequencing; precision medicine; pan-cancer Received: March 06, 2021     Accepted: March 28, 2021     Published: April 13, 2021 Copyright: © 2021 White et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT We developed and analytically validated a comprehensive genomic profiling (CGP) assay, GEM ExTra, for patients with advanced solid tumors that uses Next Generation Sequencing (NGS) to characterize whole exomes employing a paired tumor-normal subtraction methodology. The assay detects single nucleotide variants (SNV), indels, focal copy number alterations (CNA), TERT promoter region, as well as tumor mutation burden (TMB) and microsatellite instability (MSI) status. Additionally, the assay incorporates whole transcriptome sequencing of the tumor sample that allows for the detection of gene fusions and select special transcripts, including AR-V7, EGFR vIII, EGFRvIV, and MET exon 14 skipping events. The assay has a mean target coverage of 180X for the normal (germline) and 400X for tumor DNA including enhanced probe design to facilitate the sequencing of difficult regions. Proprietary bioinformatics, paired with comprehensive clinical curation results in reporting that defines clinically actionable, FDA-approved, and clinical trial drug options for the management of the patient’s cancer. GEM ExTra demonstrated analytic specificity (PPV) of > 99.9% and analytic sensitivity of 98.8%. Application of GEM ExTra to 1,435 patient samples revealed clinically actionable alterations in 83.9% of reports, including 31 (2.5%) where therapeutic recommendations were based on RNA fusion findings only.