Genetic Instability Markers in Cancer.
Methods Mol Biol
; 2055: 133-154, 2020.
Article
em En
| MEDLINE
| ID: mdl-31502150
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Instabilidade de Microssatélites
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article