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Sentinel node biopsy (SNB) is a main staging biomarker in melanoma and is the first lymph node to drain the tumor, thus representing the immunological site where anti-tumor immune dysfunction is established and where potential prognostic immune markers can be identified. Here we analyzed microRNA (miR) profiles in archival tumor-positive SNBs derived from melanoma patients with different outcomes and performed an integrated analysis of transcriptional data to identify deregulated immune signaling networks. Twenty-six miRs were differentially expressed in melanoma-positive SNB samples between patients with disease progression and non-progressing patients, the majority being previously reported in the regulation of immune responses. A significant variation in miR expression levels was confirmed in an independent set of SNB samples. Integrated information from genome-wide transcriptional profiles and in vitro assessment in immune cells led to the identification of miRs associated with the regulation of the TNF receptor superfamily member 8 (TNFRSF8) gene encoding the CD30 receptor, a marker increased in lymphocytes of melanoma patients with progressive disease. These findings indicate that miRs are involved in the regulation of pathways leading to immune dysfunction in the sentinel node and may provide valuable markers for developing prognostic molecular signatures for the identification of stage III melanoma patients at risk of recurrence. [ABSTRACT FROM AUTHOR]

Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele-specific hyper-methylation and down-regulation of gene expression. [ABSTRACT FROM AUTHOR]

Prostaglandins, especially prostaglandin E synthetase ( PGE2), influence carcinogenesis by promoting cell proliferation, inhibiting apoptosis, stimulating angiogenesis and mediating immune suppression. Cyclooxygenase-2, coded by the PTGS2 gene, is the key enzyme in the production of prostaglandins. In melanoma, Cox-2 is over expressed in primary malignant melanoma ( MM) and in their corresponding metastases. Polymorphisms in the promoter region of PTGS2 gene can modulate gene expression and could modify individual susceptibility to MM. Two hundred and forty melanoma patients and 342 controls were genotyped for polymorphisms −765 G> C (rs20417) and −1195 A> G (rs689466). Allele −765 C frequency was significantly higher in melanoma patients. No allele frequency differences for −1195 A> G polymorphism were observed. Haplotype analysis revealed that the haplotypes carrying the minor alleles were associated to a higher risk of melanoma ( P = 0.02). Expression analysis showed that allele −765 C is associated to a higher gene expression and could represent a risk allele by affecting the functionality of the promoter. [ABSTRACT FROM AUTHOR]

The article discusses research about the link between the polymorphism of micro RNA 146a and melanoma risk in a patient population in Italy. Topics mentioned include the role of epigenetics in the development and progression of melanoma, the regulation of proto-oncogene expression or tumor suppressor gene expression by microRNA, and the use of a logistic regression coding the genotypes.