Frontiers in Oncology (Dec 2018)

Molecular and Computational Methods for the Detection of Microsatellite Instability in Cancer

  • Laura G. Baudrin,
  • Laura G. Baudrin,
  • Jean-François Deleuze,
  • Jean-François Deleuze,
  • Alexandre How-Kit

DOI
https://doi.org/10.3389/fonc.2018.00621
Journal volume & issue
Vol. 8

Abstract

Read online

Microsatellite instability (MSI) is a genomic alteration in which microsatellites, usually of one to four nucleotide repeats, accumulate mutations corresponding to deletions/insertions of a few nucleotides. The MSI phenotype has been extensively characterized in colorectal cancer and is due to a deficiency of the DNA mismatch repair system. MSI has recently been shown to be present in most types of cancer with variable frequencies (from <1 to 30%). It correlates positively to survival outcome and predicts the response to immune checkpoint blockade therapy. The different methods developed for MSI detection in cancer require taking into consideration two critical parameters which influence method performance. First, the microsatellite markers used should be chosen carefully to ensure they are highly sensitive and specific for MSI detection. Second, the analytical method used should be highly resolute to allow clear identification of MSI and of the mutant allele genotype, and should present the lowest limit of detection possible for application in samples with low mutant allele frequency. In this review, we describe all the different molecular and computational methods developed to date for the detection of MSI in cancer, how they have evolved and improved over the years, and their advantages and drawbacks.

Keywords