Microsatellite instability

Author: Prof. Dr. med. Peter Altmeyer

Last updated on: 26.11.2022

Synonym(s)

MSI

Definition
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Microsatellites are short stretches of DNA that are characterized by simple repetition patterns of the underlying building blocks. If errors occur in the structure of these microsatellites during cell division, certain repair proteins, e.g. DNA polymerases, detect and correct this faulty structure (e.g. faulty base sequences = mismatch) during DNA replication (see DNA repair).

These polymerases carry out a so-called "mismatch repair". If this correction mechanism is disturbed, e.g. by mutations of the genes coding for these repair proteins (hMLH1, hMSH2, hMSH6, hPMS1, hPMS2), the microsatellites deviate from their normal length after the faulty division because "building blocks" have been exchanged or are missing. If different lengths of microsatellites are encountered in a tumor tissue, the term "microsatellite instability" (MSI) is used.

Microsatellite instability is typically found in tumors from the hereditary colorectal cancer without generalized polyposis (HNPCC) form. Microsatellite instability testing is common in hereditary colon carcinoma of the non-polyposis type or in Muir-Torre syndrome, a minus variant of HNPCC.

Classification
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MSI-H - from MSI-high (high-grade MSI)

MSI-L - from MSI-low (low-grade MSI)

MSS - from microsatellite stability (microsatellite stable)

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Diagnostics
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Currently, hardly any biomarker in oncology is applied clinically as broadly as microsatellite instability: It affects the important clinical aspects of cancer risk, prognosis and therapy prediction.

MSI as a predictive marker: Microsatellite unstable tumors respond particularly well to checkpoint-directed immunotherapy. MSI is therefore an established predictive biomarker for the efficacy of treatment with immune checkpoint inhibitors.

Naturopathy
This section has been translated automatically.

Microsatellites are short sections of DNA, which are characterized by simple repetition patterns of the underlying building blocks: If errors in the structure of these microsatellites occur during cell division, certain repair proteins, e.g. DNA polymerases, detect and correct this faulty structure (e.g. faulty base sequences = mismatch) during DNA replication. These polymerases carry out a process known as mismatch repair. If this correction mechanism is disturbed, e.g. by mutations of the genes coding for these repair proteins (hMLH1, hMSH2, hMSH6, hPMS1, hPMS2), the microsatellites deviate from their normal length after the faulty division because "building blocks" have been exchanged or are missing. If different lengths of the microsatellites are found in a tumour tissue, this is called "microsatellite instability" (MSI). Microsatellite instability is typically found in tumors of the HNPCC form, and since DNA is more frequently replicated in tumors than in other cells, microsatellite instability can be detected by comparing DNA sequences (microsatellite markers) from a tumor and other DNA from the same organism. If it actually occurs in the examined tumour, it can be assumed that the patient has a genetic defect in the DNA repair system and that this is the reason for the development of a malignancy. Since this genetic defect can be inherited, genetic counselling and extended precautions for the patient and his relatives are recommended. The examination for microsatellite instability is common in diseases of hereditary colorectal carcinoma of the non-polyposis type (HNPCC = hereditary colorectal carcinoma without generalized polyposis) or Muir-Torre syndrome, a minus variant of HNPCC.

Note(s)
This section has been translated automatically.

Since DNA is replicated more frequently in tumor cells than in other cells, microsatellite instability can be detected by comparing DNA sequences (microsatellite markers) from a tumor and another DNA from the same organism. If it actually occurs in the examined tumour, it can be assumed that the patient has a genetic defect in the DNA repair system and that this is the reason for the development of a malignoma. Since this genetic defect can be inherited, genetic counselling and extended precautions for the patient and his relatives are advisable.

Literature
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Deqin M et al (2012) Somatic Deletions of the PolyA Tract in the 3' Untranslated Region of Epidermal Growth Factor Receptor Are Common in Microsatellite Instability-High Endometrial and Colorectal Carcinomas. Arch Catholic Lab Med 136:510-516
Heinimann K (2000): Molecular genetic diagnosis of HNPCC (hereditary colorectal carcinoma without generalized polyposis). Swiss medical journal 36: 2009-2012