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Journal Article
Review
Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer.
Microsatellite instability (MSI) is a molecular hallmark for some colorectal cancers (CRCs) in which short tandem repeats are prone to mutations along with DNA sequences. It is due to DNA-mismatch-repair system deficiency because of a germline/somatic mutation in mismatch-repair (MMR) genes. The germline mutations lead to Lynch syndrome (LS) while epigenetic gene silencing results in sporadic CRC tumors. We discuss in our paper the most important clinical aspects of MSI testing in CRCs. We reviewed the most reliable relevant studies and clinical trials according to their high-quality methods, particularly within two recent decades. MSI testing is used to classify CRC tumors as MSI-high (MSI-H), MSI-low, and microsatellite stable tumors. MSI-H or MMR deficient tumors have shown the best prognosis among all CRCs, so MSI testing is considered as a good prognostic marker. Moreover, it is used to identify LS among familial CRC patients. There is a diagnostic mutation in BRAF gene (V600E) by which sporadic CRCs could be distinguished from LS associated CRCs, due to its concordance with sporadic CRCs not LS. Although, some previous studies had demonstrated a predictive role for MSI testing in chemotherapy process, emerging some controversial findings in recent studies has not convinced many authors to recommend it as a routine examination to evaluate therapeutic response. Though emerging new molecular findings have opened novel windows to develop clinical management of CRC, MSI testing has remained as an excellent prognostic and diagnostic tool for CRC tumors.
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