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An Automated Method to Perform The In Vitro Micronucleus Assay using Multispectral Imaging Flow Cytometry
Published on: May 13, 2019
"Micronuclei and Disease" special issue: Aims, scope, and synthesis of outcomes
Michael Fenech1, Siegfried Knasmueller2, Lisbeth E Knudsen3
1Health and Biomedical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, 5000, Australia; Genome Health Foundation, North Brighton, SA, 5048, Australia; Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia.
Abstract:
The purpose of the "Micronuclei and Disease" special issue (SI) is to: (i) Determine the level of evidence for association of micronuclei (MN), a biomarker of numerical and structural chromosomal aberrations, with risk of specific diseases in humans; (ii) Define plausible mechanisms that explain association of MN with each disease; (iii) Identify knowledge gaps and research needed to translate MN assays into clinical practice. The "MN and Disease" SI includes 14 papers. The first is a review of mechanisms of MN formation and their consequences in humans. 11 papers are systematic reviews and/or meta-analyses of the association of MN with reproduction, child health, inflammation, auto-immune disease, glycation, metabolic diseases, chronic kidney disease, cardiovascular disease, eleven common cancers, ageing and frailty. The penultimate paper focuses on effect of interventions on MN frequency in the elderly. A road map for translation of MN data into clinical practice is the topic of the final paper. The majority of reviewed studies were case-control studies in which the ratio of mean MN frequency in disease cases relative to controls, i.e. the mean ratio (MR), was calculated. The mean of these MR values, estimated by meta-analyses, for lymphocyte and buccal cell MN in non-cancer diseases were 2.3 and 3.6 respectively, and for cancers they were 1.7 and 2.6 respectively. The highest MR values were observed in studies of cancer cases in which MN were measured in the same tissue as the tumour (MR = 4.9-10.8). This special issue is an important milestone in the evidence supporting MN as a reliable genomic biomarker of developmental and degenerative disease risk. These advances, together with results from prospective cohort studies, are helping to identify diseases in which MN assays can be practically employed in the clinical setting to better identify high risk patients and to prioritise them for preventive therapy.
Insights
Micronuclei (MN), a biomarker for chromosomal damage, are linked to various diseases. This special issue reviews evidence, mechanisms, and clinical applications for MN assays in disease risk assessment and patient stratification.
Area of Science:
- Genomic Biomarkers
- Disease Risk Assessment
- Clinical Translation
Background:
- Micronuclei (MN) are indicators of chromosomal aberrations.
- Evidence linking MN to human disease risk requires comprehensive evaluation.
- Translating MN assays into clinical practice necessitates defining mechanisms and research gaps.
Purpose of the Study:
- To assess the evidential support for MN association with specific human diseases.
- To elucidate mechanistic pathways connecting MN to disease pathogenesis.
- To identify research priorities for implementing MN assays in clinical settings.
Main Methods:
- Systematic reviews and meta-analyses of 14 papers.
- Analysis of case-control studies calculating mean ratios (MR) of MN frequency.
- Review of mechanisms, disease associations, and clinical translation strategies for MN.
Main Results:
- Meta-analyses showed mean ratios (MR) for lymphocyte and buccal cell MN in non-cancer diseases (2.3 and 3.6) and cancers (1.7 and 2.6).
- Highest MR values (4.9-10.8) were found in cancer studies measuring MN in tumor tissue.
- The special issue provides a milestone in evidence supporting MN as a genomic biomarker for disease risk.
Conclusions:
- MN assays show promise for identifying high-risk patients for preventive therapies.
- Further research, including prospective cohort studies, is crucial for clinical application.
- This special issue advances the understanding and utility of MN in disease risk prediction.

