|LETTER TO THE EDITOR
|Ahead of print publication
Microsatellite instability in colorectal cancer from causes to detection
Meysam Mosallaei, Miganoosh Simonian, Rasool Salehi
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Colorectal cancer (CRC) is known as one of the common malignancies in worldwide. Several studies indicated that 20% of patients have a potential causal genetic component. About 15% to 20% of sporadic colorectal cancer (SCC) and most (90%) patients with Lynch syndrome show microsatellite instability (MSI). MSI is characterized by length alterations within simple repeated sequences, microsatellites. Lynch syndrome results from germline mutations in one or more mismatch repair (MMR) genes including hMLH1 or hMSH2 and less frequently hMSH6 or hPMS2, and CpG island methylator phenotype (high especially in MLH1 and MSH2) has been seen in 15% of sporadic colorectal. Replication error and microsatellites status are key indicators for discrimination between SCC, hereditary CRC, and familial cancer risk appraisal. On the other hand, studies revealed that MMR-deficient CRC cells show significantly reduced sensitivity to fluorouracil and to a variety of clinically important drugs. Thus, MSI assessments considered as a prognostic and predictor marker.
The current standard method of MSI analysis using five quasi-mononucleotide markers (BAT-26, BAT-25, NR-24, NR-21, and NR-27) is still time-consuming and expensive. Hence, in many research, it has been replaced with the other panels including 3, 2, or 1 marker. Appropriate microsatellites are amplified by polymerase chain reaction using fluorescently labeled primers, and then, fragment length polymorphisms are identified through capillary electrophoresis. In this method, the choice of standard markers is important since they are monomorphic at the population level and highly unstable in target. Next-generation sequencing (NGS) as a new diagnostic method allows many genes to be sequenced simultaneously for each patient with higher sensitivity for low-prevalence mutations, including genes of interest such as MMR genes. However, because the majority of sporadic MSI-positive tumors often result from epigenetic changes rather than mutations in target genes, even fully sequencing by NGS will not provide sufficient data to reliably infer MSI status in a tumor. Alternatively, it can be used bisulfite sequencing analysis for detection of DNA methylation patterns or microsatellite instability detection by next generation sequencing (mSINGS).
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Mosallayi M, Simonian M, Khosravi S, Salehi AR, Khodadoostan M, Sebghatollahi V, et al.
Polymorphism (Rs16917496) at the miR-502 binding site of the lysine methyltransferase 5A (SET8) and its correlation with colorectal cancer in Iranians. Adv Biomed Res 2017;6:77.
] [Full text]
Søreide K. High-fidelity of five quasimonomorphic mononucleotide repeats to high-frequency microsatellite instability distribution in early-stage adenocarcinoma of the colon. Anticancer Res 2011;31:967-71.
Babaei H, Zeinalian M, Emami MH, Hashemzadeh M, Farahani N, Salehi R, et al.
Simplified microsatellite instability detection protocol provides equivalent sensitivity to robust detection strategies in Lynch syndrome patients. Cancer Biol Med 2017;14:142-50.
Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem 2014;60:1192-9.