Microsatellite Instability Detection: The Current Standards, Limitations, and Misinterpretations

Article Tools REVIEW ARTICLES Diagnostics Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/PO.23.00010 JCO Precision Oncology no. 7 (2023) e2300010. Published online June 14, 2023. PMID: 37315263 Microsatellite Instability Detection: The Current Standards, Limitations, and Misinterpretations Valentina Yakushina , PhD1,2xValentina YakushinaSearch for articles by this author; Alexandra Kavun , MSc1xAlexandra KavunSearch for articles by this author; Egor Veselovsky, MSc1,3xEgor VeselovskySearch for articles by this author; Tatiana Grigoreva , MSc1,4xTatiana GrigorevaSearch for articles by this author; Ekaterina Belova , PhD1,5xEkaterina BelovaSearch for articles by this author; Alexandra Lebedeva , MSc1xAlexandra LebedevaSearch for articles by this author; Vladislav Mileyko , MSc1xVladislav MileykoSearch for articles by this author; and Maxim Ivanov , PhD1,6xMaxim IvanovSearch for articles by this author Show More 1OncoAtlas LLC, Moscow, Russian Federation2Laboratory of Epigenetics, Research Centre for Medical Genetics, Moscow, Russian Federation3Department of Evolutionary Genetics of Development, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, Moscow, Russian Federation4Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation5Lomonosov Moscow State University, Moscow, Russian Federation6Moscow Institute of Physics and Technology, Moscow, Russian Federation https://doi.org/10.1200/PO.23.00010 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyCONTEXTKey ObjectiveAccurate microsatellite instability (MSI) assessment is critical for Lynch syndrome diagnostics, prognosis of disease progression, and success of chemotherapy and immunotherapy. In immunotherapy, false-positive MSI testing prevents putative responding patients from receiving effective treatment, and false-negative MSI testing leads to the prescription of ineffective therapy with its adverse effects.Knowledge GeneratedThis article provides the main advantages and limitations of the standard MSI testing methods and novel approaches in clinical practice, assesses possible sources of errors, discusses best practices and guidelines, and highlights the unsolved questions that remain sources of incorrect interpretation.RelevanceAmong novel approaches, next-generation sequencing (NGS) is considered one of the most promising; its advantages include high accuracy, an expanded spectrum of microsatellites analyzed, and simultaneous assessment of a comprehensive spectrum of clinically significant markers. In liquid biopsy, NGS-based approaches demonstrate outstanding results.SUPPORTSupported by the Russian Science Foundation (project No. 22-75-10154; https://rscf.ru/project/22-75-10154/).AUTHOR CONTRIBUTIONSConception and design: Valentina Yakushina, Vladislav Mileyko, Maxim IvanovData analysis and interpretation: Alexandra Kavun, Egor Veselovsky, Tatiana Grigoreva, Ekaterina Belova, Alexandra LebedevaManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Valentina YakushinaEmployment: Atlas OncodiagnosticsAlexandra KavunEmployment: OncoAtlas LLCEgor VeselovskyEmployment: OncoAtlas LLCTatiana GrigorevaEmployment: OncoAtlas LLCEkaterina BelovaEmployment: OncoAtlas LLCAlexandra LebedevaEmployment: OncoAtlas LLCVladislav MileykoEmployment: OncoAtlas LLCLeadership: OncoAtlas LLCStock and Other Ownership Interests: OncoAtlasResearch Funding: I-pharmMaxim IvanovEmployment: OncoAtlas LLCNo other potential conflicts of interest were reported.