EMQN best practice guidelines for analysis and reporting of microsatellite instability in solid tumours

Journal article : Review

Microsatellite instability (MSI) is the accumulation of insertion and deletion variants (instability) in short tandem repeat DNA sequences (microsatellites). High levels of MSI occur following loss of function of the DNA mismatch repair system (MMR). MMR deficiency is an increasingly important cancer biomarker that is associated with chemotherapy resistance and response to immune checkpoint blockade, as well as one of the commonest hereditary cancer syndromes, Lynch syndrome. Since its discovery over two decades ago, our biological understanding, the testing methods, and the clinical implications of MSI analysis have expanded rapidly and up-to-date best practice guidelines are needed. An expert working group reviewed the literature and devised 15 best practice recommendations that were finalised following consultation with clinical and laboratory scientists partnered with EMQN. These include seven recommendations on key technical aspects of MSI testing and eight recommendations on the clinical interpretation and reporting of results. The latter focuses on Lynch syndrome screening and immune checkpoint blockade therapy. Example report wording is provided to assist implementation and standardisation. Common terminology and MSI analysis methods are also discussed. These guidelines are aimed primarily at genomic scientists working in diagnostic testing laboratories, but will provide a useful review of MSI for clinicians, academics, and other related professionals.

Authors: Gallon, R; McCormick, L; Saetta, A; Albuquerque, C; Butler, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: European Journal of Human Genetics
• Volume: 34
• Issue: 1
• Pages: 134-146
• Publication date: 2025-08-20
• Acceptance date: 2025-07-08
• DOI: 10.1038/s41431-025-01913-x
• EISSN: 1476-5438
• ISSN: 1018-4813
• Language: English
• Keywords: Microsatellite instability; Lynch syndrome; Best practice; Medicine; DNA mismatch repair; Microsatellite; Cancer genetics; Terminology; Clinical Practice; Genetic testing; Cancer; Genetics; Biology; Internal medicine; Family medicine; Political science
• Subtype: Review