Pan-cancer microsatellite instability testing using a multiplex assay including long mononucleotide repeats.

• DOI: 10.1200/jco.2025.43.4_suppl.290
• Publication Date: 2025-01-27T14:33:47Z
• Authors: Dustin A. Deming; Jeff Bacher; Irina Vyazunova; Dawn Albrecht; Madeleine Buratti; Laura Ruelle; Cheri Pasch; Santina Snow; Kristina Matkowskyj; Ryan Sappenfield; Richard Halberg
• Keywords: Multiplex; Microsatellite Instability

290 Background: Microsatellite instability (MSI)/mismatch repair deficiency (dMMR) testing is a critical component of molecular for gastrointestinal cancers, among others. These analyses are important the identification patients with lynch syndrome and eligibility treatment immunotherapy. The current standard care can identify most cases, however improved MSI-H status needed non-colorectal cancers alterations outside MLH1/PMS2. A recent analysis indicated potential detection multiplex assay including long mononucleotide repeats (LMR). Methods: Patients were selected based on MSI status, MMR gene variants, or presence high tumor mutation burden consented participation as part an IRB-approved protocol (UW15068). Formalin-fixed tissue slides annotated by pathologist normal tissue. Slides scraped DNA isolated. LMR Analysis System (Promega, Madison, WI) OncoMate Dx (Promega) performed cancer when available per manufacturer’s protocols. Instability microsatellites score reported correlated clinical immunohistochemistry (IHC) commercial next-generation sequencing (NGS). Results: total 96 samples tested across 94 over 20 different types, lung, colon, rectal, gynecologic, esophagogastric cancers. Tumors from known to have microsatellite NGS testing. 27 cases found be assay. All these also additional 3 using only Of all stable NGS. This number includes 1 colorectal 2 cases. One was loss MSH6 IHC (MSH6 L1061fs). intact IHC, though did exon 7 splice acceptor alteration that failed calling quality control. last case not performed, no detected alterations, 6.3 mutations megabase. Conclusions: In this limited dataset, utility various methods determination MSI, dMMR, TMB PCR, demonstrated patient cohort spanning solid types. Promising results observed System. findings need further validated in larger dataset response immunotherapeutics.