Cited by 1,063Genetic factors in colorectal cancerColorectal Cancer Treatments and StudiesColorectal Cancer Surgical Treatments

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Microsatellite Instability in Colorectal Cancer-the Stable Evidence

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Vilar, Eduardo, Gruber, Stephen B.·2010·Nature Reviews Clinical Oncology

DOI 10.1038/nrclinonc.2009.237PMC PMC3427139

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Abstract

Microsatellite instability (MSI) is the molecular fingerprint of a deficient mismatch repair system. Approximately 15% of colorectal cancers (CRC) display MSI owing either to epigenetic silencing of MLH1 or a germline mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2. Methods to detect MSI are well established and routinely incorporated into clinical practice. A clinical and molecular profile of MSI tumors has been described, leading to the concept of an MSI phenotype in CRC. Studies have confirmed that MSI tumors have a better prognosis than microsatellite stable CRC, but MSI cancers do not necessarily have the same response to the chemotherapeutic strategies used to treat microsatellite stable tumors. Specifically, stage II MSI tumors might not benefit from 5-fluorouracil-based adjuvant chemotherapy regimens. New data suggest possible advantages of irinotecan-based regimens, but these findings require further clarification. Characterization of the molecular basis of MSI in CRC is underway and initial results show that mutations in genes encoding kinases and candidate genes with microsatellite tracts are over-represented in MSI tumors. Transcriptome expression profiles of MSI tumors and systems biology approaches are providing the opportunity to develop targeted therapeutics for MSI CRC.

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Authors: Vilar, E., & Gruber, S. B.
Affiliations: University of Michigan (US)
Corresponding author: Gruber, Stephen B.
ORCID: Vilar, Eduardo
Gruber, Stephen B.
Venue: Nature Reviews Clinical Oncology
Publisher: Springer Science and Business Media LLC
Published: 2010-02-09
Volume: 7
Issue: 3
Pages: 153-162
ISSN: 1759-4774 (ISSN-L)
1759-4782
DOI: 10.1038/nrclinonc.2009.237
PMC: PMC3427139
OpenAlex: W2050658928
Cited by: 1,063
References: 100
Citations by year: 2026: 57 · 2025: 100 · 2024: 116 · 2023: 114 · 2022: 99 · 2021: 81 · 2020: 75 · 2019: 65 · 2018: 66 · 2017: 46 · 2016: 34 · 2015: 47 · 2014: 44 · 2013: 44 · 2012: 28
FWCI: 4.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (5P30 CA 46592, 1R01CA81488, R01CA081488, P30CA046592)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
Keywords: microsatellite instability, colorectal cancer, mismatch repair deficiency, prognosis, predictive biomarkers, irinotecan, kinase mutations, targeted therapy
MeSH terms: DNA Repair, Humans, Colorectal Neoplasms, Germ-Line Mutation, DNA Repair Enzymes, Microsatellite Instability

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