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Review
. 2023 Jan 25;14(1):143-165.
doi: 10.1007/s13167-023-00312-w. eCollection 2023 Mar.

Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook

Jakub Styk  1   2   3 , Zuzana Pös  2   3   4 , Ondrej Pös  2   3 , Jan Radvanszky  2   4   5 , Evelina Hrckova Turnova  2   6 , Gergely Buglyó  7 , Daniela Klimova  1 , Jaroslav Budis  2   3   8 , Vanda Repiska  1   9 , Bálint Nagy  2   7 , Tomas Szemes  2   3   5
Affiliations
Review

Microsatellite instability assessment is instrumental for Predictive, Preventive and Personalised Medicine: status quo and outlook

Jakub Styk et al. EPMA J. .

Abstract

A form of genomic alteration called microsatellite instability (MSI) occurs in a class of tandem repeats (TRs) called microsatellites (MSs) or short tandem repeats (STRs) due to the failure of a post-replicative DNA mismatch repair (MMR) system. Traditionally, the strategies for determining MSI events have been low-throughput procedures that typically require assessment of tumours as well as healthy samples. On the other hand, recent large-scale pan-tumour studies have consistently highlighted the potential of massively parallel sequencing (MPS) on the MSI scale. As a result of recent innovations, minimally invasive methods show a high potential to be integrated into the clinical routine and delivery of adapted medical care to all patients. Along with advances in sequencing technologies and their ever-increasing cost-effectiveness, they may bring about a new era of Predictive, Preventive and Personalised Medicine (3PM). In this paper, we offered a comprehensive analysis of high-throughput strategies and computational tools for the calling and assessment of MSI events, including whole-genome, whole-exome and targeted sequencing approaches. We also discussed in detail the detection of MSI status by current MPS blood-based methods and we hypothesised how they may contribute to the shift from conventional medicine to predictive diagnosis, targeted prevention and personalised medical services. Increasing the efficacy of patient stratification based on MSI status is crucial for tailored decision-making. Contextually, this paper highlights drawbacks both at the technical level and those embedded deeper in cellular/molecular processes and future applications in routine clinical testing.

Keywords: Cancer; Liquid biopsy; Massively parallel sequencing; Microsatellite instability; Patient stratification; Predictive Preventive Personalised Medicine (PPPM / 3PM); Screening.

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Conflict of interest statement

Competing interestsJS, ZP, OP, JR, JB and TS are employees of Geneton Ltd., participating in research and development activity that does not conflict with the content of the manuscript. VR is an employee of Medirex Group Academy n.p.o., participating in research and project activity with no potential conflict of interest to the proposed manuscript. EHT is an employee of Slovgen Ltd. and declares no conflict of interest. BN is an editorial board member of the EPMA journal, but had no involvement in, influence over, or access to the details of the peer review process of this work. All remaining authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Annual distribution of PubMed search results for the term “microsatellite instability” as of December 21, 2022. The red curve represents the number of emerging bioinformatics tools for MPS-based MSI analysis. There seems to be a correlation between the increasing number of publications and the emergence of novel tools
Fig. 2
Fig. 2
Since tissue biopsy analyses only a selected portion of the tumour, it may not capture its overall heterogeneity (only blue cells). As DNA from the entire tumour enters the bloodstream, liquid biopsy is able to capture ctDNA from all populations of tumour cells (red, green and blue cells). Given that MPS strategies can capture several MS markers in a single assay, these methods, combined with liquid biopsy, are the most representative approach for the personalisation of MSI detection (Created with BioRender.com)
See this image and copyright information in PMC

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