MSH2 Overexpression Due to an Unclassified Variant in 3'-Untranslated Region in a Patient with Colon Cancer.
Lynch syndrome
MMR complex deficiency
MMR gene
MSH2 3’UTR variant
MSH2 protein
MSH2 unclassified variants
hereditary colon cancer
over expression MSH2
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
19 Jun 2020
19 Jun 2020
Historique:
received:
13
05
2020
revised:
14
06
2020
accepted:
16
06
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
25
6
2020
Statut:
epublish
Résumé
The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated or rearranged in Lynch syndrome (LS), which is characterized by a high risk of tumor development, including colorectal cancer. However, many variants identified in this gene are often defined as variants of uncertain significance (VUS). In this study, we selected a variant in the 3' untranslated region (UTR) of MSH2 (c*226A > G), identified in three affected members of a LS family and already reported in the literature as a VUS. The effect of this variant on the activity of the MMR complex was examined using a set of functional assays to evaluate MSH2 expression. We found MSH2 was overexpressed compared to healthy controls, as determined by RTqPCR and Western blot analyses of total RNA and proteins, respectively, extracted from peripheral blood samples. These results were confirmed by luciferase reporter gene assays. We therefore speculated that, in addition to canonical inactivation via a gene mutation, MMR activity may also be modulated by changes in MMR gene expression.
Sections du résumé
BACKGROUND
BACKGROUND
The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated or rearranged in Lynch syndrome (LS), which is characterized by a high risk of tumor development, including colorectal cancer. However, many variants identified in this gene are often defined as variants of uncertain significance (VUS). In this study, we selected a variant in the 3' untranslated region (UTR) of MSH2 (c*226A > G), identified in three affected members of a LS family and already reported in the literature as a VUS.
METHODS
METHODS
The effect of this variant on the activity of the MMR complex was examined using a set of functional assays to evaluate MSH2 expression.
RESULTS
RESULTS
We found MSH2 was overexpressed compared to healthy controls, as determined by RTqPCR and Western blot analyses of total RNA and proteins, respectively, extracted from peripheral blood samples. These results were confirmed by luciferase reporter gene assays.
CONCLUSIONS
CONCLUSIONS
We therefore speculated that, in addition to canonical inactivation via a gene mutation, MMR activity may also be modulated by changes in MMR gene expression.
Identifiants
pubmed: 32575404
pii: biomedicines8060167
doi: 10.3390/biomedicines8060167
pmc: PMC7345785
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Fondo straordinario di Ateneo Federico II
ID : 2018
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