Genetic Instability Markers in Cancer

  • Giuseppe Palmieri
  • Milena Casula
  • Antonella Manca
  • Grazia Palomba
  • Maria Cristina Sini
  • Valentina Doneddu
  • Antonio Cossu
  • Maria Colombino
Part of the Methods in Molecular Biology book series (MIMB, volume 2055)


High frequency of mutations seems to determine a higher occurrence of neoepitope formation and, thus, tumor immunogenicity. A somatic hypermutated status could thus act as a predictive biomarker of responsiveness to immunotherapy with recent immune checkpoint inhibitors. Among several factors involved in determining the hypermutated status, such as inactivating mutations in the DNA polymerases as well as exposure to external (cigarette smoke, UV radiation, chemicals) and endogenous (reactive oxygen species) mutagens, a defective DNA mismatch repair system may give rise to genetic instability and, particularly, to microsatellite instability (MSI). The occurrence of MSI has been associated with increased load of mutations and expression of abundant peptides that serve as neoantigens to elicit an immune response within a context of a favorable tumor microenvironment. Here we describe methodological strategies to investigate for the presence of the MSI phenotype in cancer samples, through a combination of molecular approaches performed on paraffin-embedded tissues.

Key words

Microsatellite instability Defective mismatch repair Response to immunotherapy 



This work was partially supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) “Programma di ricerca 5 per Mille 2018—Id.21073.”

Conflict of Interest: The authors have no conflict of interest to declare.

Author Contributions: GiP: Conception and design, acquisition of protocol data, drafting the manuscript. MiC, AM, GrP, MCS: Analysis and interpretation of molecular protocols, revising the manuscript. VD, AC: Analysis and interpretation of pathology aspects, revising the manuscript. MaC: Conception and design, contributed unpublished essential data or protocols, revising the manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Giuseppe Palmieri
    • 1
  • Milena Casula
    • 1
  • Antonella Manca
    • 1
  • Grazia Palomba
    • 1
  • Maria Cristina Sini
    • 1
  • Valentina Doneddu
    • 2
  • Antonio Cossu
    • 2
  • Maria Colombino
    • 1
  1. 1.Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB)National Research Council (CNR)SassariItaly
  2. 2.University Hospital Health UnitAzienda Ospedaliero Universitaria (AOU)SassariItaly

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