DSS1 promoter hypomethylation and overexpression predict poor prognosis in melanoma and squamous cell carcinoma patients.
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 of 130 cutaneous melanomas (86.1%), 41 of 64 uveal melanomas (64.1%), 67 of 82 mucosal melanomas (81.7%), and 61 of 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.
Department of Biomedical Sciences and of Morphological and Functional Images, University of Messina, Messina, Italy 98125.
Mario
M
Venza
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy 98125.
Maria
M
Visalli
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy 98125.
Teresa
T
Catalano
Department of Human Pathology of Adult and Developmental Age "Gaetano Barresi", University of Messina, Messina, Italy 98125; Scylla Biotech Srl, University of Messina, Messina, Italy 98125.
Concetta
C
Beninati
Charybdis Vaccines Srl, University of Messina, Messina, Italy 98125.
Diana
D
Teti
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy 98125. Electronic address: isavenza@gmail.com.
Isabella
I
Venza
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014604:Uveal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000098943:Uveal Melanoma
D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; C484606:SEM1 protein, human; D000077209:Decitabine; D015254:DNA Modification Methylases; D046988:Proteasome Endopeptidase Complex; D001374:Azacitidine
DSS1; Hypomethylation; Melanoma; Overexpression; Squamous cell carcinoma