Minimizing Sample Failure Rates for Challenging Clinical Tumor Samples

Abstract

Identification of somatic variants in cancer by high-throughput sequencing has become common clinical practice largely because many of these variants may be predictive biomarkers for targeted therapies. However, there can be high sample quality control (QC) failure rates for some tests preventing the return of results. SLIMamp is a patented technology that has been incorporated into commercially available cancer NGS testing kits with the claimed advantage that these kits can interrogate challenging formalin-fixed paraffin-embedded tissue (FFPET) samples with low tumor purity, poor DNA quality, and/or low input DNA, resulting in a high sample QC pass rate. The aim of this study was to substantiate that claim using Pillar's oncoReveal Solid Tumor Panel. 48 samples that had failed one or more pre-analytical QC sample parameters for whole exome sequencing (WES) from ATGC's ISO15189 accredited diagnostic genomics laboratory were acquired. XING Genomic Services (XGS) performed an exploratory data analysis to characterize the samples and then tested the samples in their ISO15189 accredited laboratory. Clinical reports could be generated for 37 samples (77%), of which 29 (60%) contained clinically actionable or significant variants that would not have otherwise been identified. 11 samples were deemed to be unreportable and the sequencing data were likely dominated by artefacts. A novel post-sequencing QC metric was developed which can discriminate between clinically reportable and unreportable samples.