Mismatch repair deficiency: The what, how and why it is important

Genes Chromosomes Cancer. 2022 Jun;61(6):314-321. doi: 10.1002/gcc.23015. Epub 2021 Dec 9.


The mismatch repair system is a major pathway that functions in the maintenance of genomic integrity. It is involved in mitotic and meiotic recombination, apoptosis, immunoglobulin gene rearrangement, somatic hypermutation, and other processes. Deficiencies in mismatch repair give rise to hypermutability and the phenomenon called microsatellite instability. Detection of deficient mismatch repair function or microsatellite instability is used diagnostically, predictively, and prognostically. Specifically, deficient mismatch repair function is used for screening of Lynch syndrome, determining patients who are likely to respond to immune checkpoint inhibition, and to contributes to an understanding of which cancer patients may pursue a more aggressive clinical course. Microsatellite instability can be evaluated directly by polymerase chain reaction (PCR) or indirectly by assessment of mismatch repair protein expression using immunohistochemistry (IHC), and mismatch repair function using next-generation sequencing assays which evaluates homopolymer indels. In this article, we provide a concise practical review on mismatch repair deficiency (MMR-d)/microsatellite instability (MSI), focusing on clinical testing, different testing methods, interpretation of findings, the predictive, and prognostic utility of MSI.

Keywords: Lynch syndrome; PD-1; colorectal carcinoma; endometrial carcinoma; immune checkpoint inhibition; microsatellite instability (MSI); mismatch repair; mismatch repair deficiency (d-MMR).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / genetics
  • DNA Mismatch Repair / genetics
  • Humans
  • Microsatellite Instability
  • Neoplastic Syndromes, Hereditary*

Supplementary concepts

  • Turcot syndrome