Identification of Actionable Genomic Alterations in Tissue Using Idylla™

Abstract

Quick and reliable identification of actionable genomic alterations is essential to providing high‐quality cancer care. Herein we describe our assessment of Idylla™, a fully automated, cartridge‐based, PCR system for the qualitative detection of actionable genomic alterations in formalin‐fixed, paraffin‐embedded (FFPE) tissue. Three different Idylla™ assays were evaluated to demonstrate the system's ease of use, concordance with established methodology, and overall clinical utility.Thirty‐six patient samples, previously characterized using a clinically validated method, were assessed for EGFR mutations, BRAF mutations, or microsatellite instability (MSI) using Idylla™. The Idylla™ MSI Mutation Assay, which detects mutations in seven novel, tumor specific MSI loci (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, and SULF2), was used to assess microsatellite stability in twelve cases of colorectal cancer. The Idylla™ EFGR Mutation Assay, which detects 51 mutations in exons 18, 19, 20, and 21 of the EGFR gene, was used to identify mutations in twelve cases of lung cancer. Lastly, the Idylla™ BRAF Mutation Assay, which detects seven mutations in codon 600 of the BRAF oncogene, was used to detect mutations in twelve cases of melanoma.Briefly, one 10μm FFPE tissue section was loaded into the cartridge per the manufacturer's instructions. No manual macrodissection was performed. A representative H&E stained slide was retrospectively reviewed and scored for neoplastic cell content by a Pathologist (K.H.). Idylla™ assay results were compared to previously reported results. Three cases, one per assay, were excluded from the final analysis due to lack of neoplastic cell content (NT = no tumor) or assay incompatibility.Overall, the adjusted concordance between the Idylla™ assays and clinically validated methodologies was high. The Idylla™ MSI Mutation Assay was 100% (11/11) concordant with the immunohistochemical assay for mismatch repair (MMR), which included markers MLH1, MSH2, MSH6, and PMS2. The Idylla™ EGFR and Idylla™ BRAF Mutation assays were 91% (10/11) concordant with Sanger sequencing results. Additional studies utilizing a third methodology are needed to further evaluate discordant results.The Idylla™ assays showed high concordance with previously reported results generated using clinically validated methods. Advantages of the Idylla™ system include minimal hands‐on time and rapid turnaround time. In conclusion, Idylla™ offers fast and reliable analysis for a variety of actionable genomic alterations in FFPE tissue.Support or Funding InformationSupport for this project was provided by the Department of Pathology and Laboratory Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.