Previous studies have found a link between high expression levels of the Deleted in Split hand/Split foot 1 (DSS1) gene and cancer progression. The aim of this study was to examine whether overexpression of DSS1 is a feature of melanoma and squamous cell carcinoma (SCC) and if any epigenetic modifications are involved. Evaluation of DSS1 expression profile indicated that the gene is overexpressed in 112/130 cutaneous melanomas (86.1%), 41/64 uveal melanomas (64.1%), 67/82 mucosal melanomas (81.7%), and 61/75 SCC samples (81.3%), relative to normal skin. An inverse correlation between DSS1 expression and methylation status of the promoter was found. In vitro studies showed that treatment of DSS1-methylated melanoma and SCC cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine significantly increased DSS1 expression at mRNA and protein levels. Interestingly, a significant association between high DSS1 expression levels and some clinicopathological variables, such as metastasis, ulceration, and reduced overall/disease-free survival was observed. In summary, these data suggest that the extent of promoter methylation plays a role in modulating DSS1 gene expression and highlight that promoter hypomethylation is a frequent event in melanoma and SCC closely linked to poor prognosis.

DSS1 promoter hypomethylation and overexpression predict poor prognosis in melanoma and squamous cell carcinoma patients

VENZA, Mario
Primo
;
VISALLI, Maria;CATALANO, Teresa;BENINATI, Concetta;TETI, Diana;VENZA, Isabella
Ultimo
2017-01-01

Abstract

Previous studies have found a link between high expression levels of the Deleted in Split hand/Split foot 1 (DSS1) gene and cancer progression. The aim of this study was to examine whether overexpression of DSS1 is a feature of melanoma and squamous cell carcinoma (SCC) and if any epigenetic modifications are involved. Evaluation of DSS1 expression profile indicated that the gene is overexpressed in 112/130 cutaneous melanomas (86.1%), 41/64 uveal melanomas (64.1%), 67/82 mucosal melanomas (81.7%), and 61/75 SCC samples (81.3%), relative to normal skin. An inverse correlation between DSS1 expression and methylation status of the promoter was found. In vitro studies showed that treatment of DSS1-methylated melanoma and SCC cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine significantly increased DSS1 expression at mRNA and protein levels. Interestingly, a significant association between high DSS1 expression levels and some clinicopathological variables, such as metastasis, ulceration, and reduced overall/disease-free survival was observed. In summary, these data suggest that the extent of promoter methylation plays a role in modulating DSS1 gene expression and highlight that promoter hypomethylation is a frequent event in melanoma and SCC closely linked to poor prognosis.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3097412
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