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Open AccessArticle

MSH2 Overexpression Due to an Unclassified Variant in 3’-Untranslated Region in a Patient with Colon Cancer

1
Department of Molecular Medicine and Medical Biotechnology, University Federico II, via Pansini 5, 80131 Naples, Italy
2
CEINGE-BiotecnologieAvanzate, via G. Salvatore 486, 80145 Naples, Italy
3
UOC Pathological Anatomy, Azienda Ospedaliera di Rilievo Nazionale (AORN) “A. Cardarelli”, via A. Cardarelli 9, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(6), 167; https://doi.org/10.3390/biomedicines8060167
Received: 13 May 2020 / Revised: 14 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
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: 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: 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: 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. View Full-Text
Keywords: MSH2 3’UTR variant; hereditary colon cancer; Lynch syndrome; MSH2 protein; over expression MSH2; MMR gene; MMR complex deficiency; MSH2 unclassified variants MSH2 3’UTR variant; hereditary colon cancer; Lynch syndrome; MSH2 protein; over expression MSH2; MMR gene; MMR complex deficiency; MSH2 unclassified variants
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Liccardo, R.; Nolano, A.; Lambiase, M.; Della Ragione, C.; De Rosa, M.; Izzo, P.; Duraturo, F. MSH2 Overexpression Due to an Unclassified Variant in 3’-Untranslated Region in a Patient with Colon Cancer. Biomedicines 2020, 8, 167.

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