Assessment of clinical utility and microsatellite instability detection on the Marsden360 ctDNA sequencing panel.

Abstract

e15058 Background: This project aimed to verify the Marsden360 circulating tumour DNA (ctDNA) sequencing panel for detecting microsatellite instability (MSI) in various solid cancers at The Royal Marsden Foundation Trust Clinical Genomics Department. The objective was to evaluate the sensitivity, specificity, and concordance of MSI detection, ensuring its applicability in a clinical setting. Methods: The Marsden360 panel, a 74-gene-targeted next-generation sequencing (NGS) platform, was utilised to detect MSI across 90 microsatellite loci. Samples included previously validated MSI-high (MSI-H) and microsatellite stable (MSS) plasma from different solid tumours and control synthetic plasma samples from SensID GmbH. The project employed both retrospective and prospective analyses to evaluate the panel's performance, with metrics including sensitivity, specificity, concordance, and turnaround time compared to standard PCR-based MSI testing. Results: The assay demonstrated a sensitivity and specificity of 100% for MSI detection, with 100% concordance between the Marsden360 results and those from previously validated methods. The average turnaround time for the Marsden360 was 13.9 days, significantly faster than the standard MSI testing. The panel successfully identified MSI-H status in diverse tumour types, highlighting its potential for broader clinical application. Conclusions: It proved to be a reliable and efficient tool for MSI detection in ctDNA, offering high sensitivity and specificity. Its turnaround time and ability to detect a wide range of genetic alterations make it an asset for clinical decision-making across the NHS considering its non-invasive extraction and ability to assess the full tumour heterogeneity Future studies should focus on expanding the cohort size and incorporating multi-omics approaches to enhance diagnostic accuracy and better understand the complexities of MSI in various cancer types.