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Introduction: It has been postulated that nutrition may influence the risk for cutaneous melanoma (CM); therefore, we aimed to assess the associations of food groups and individual nutrient intakes with CM in a Greek population. Methods: In this case-control study, 151 patients with histologically confirmed CM, newly diagnosed and treated in the Oncology Department of the "Laikon" University Hospital (Athens, Greece), and 151 age- and sex-matched healthy individuals residing in the Athens metropolitan area, recruited among participants for routine health examinations, were included. All participants completed a questionnaire comprising anthropometric measurements, sociodemographic, lifestyle, and health-related variables. A validated, semiquantitative food frequency questionnaire was used to assess average consumption of 136 food items during the 12 months preceding the onset of disease. Multivariate conditional regression models were used to derive odds ratios (ORs) with 95% confidence intervals (95% CI) regarding the association of nine food groups and seven macronutrients with CM. Results: Statistically significant positive associations with CM were found with higher energy intake (OR: 1.67, 95% CI: 1.22–2.30) and intake of saturated fatty acids (OR: 2.28, 95% CI: 1.00–5.28), after adjusting for sun sensitivity, major depression history, and alcohol intake. Inverse associations with higher intake of milk and dairy products (OR: 0.65, 95% CI: 0.48–0.88), fruits (OR: 0.68, 95% CI: 0.51–0.90), added lipids (OR: 0.65, 95% CI: 0.47–0.91), and sugars and syrups (OR: 0.70, 95% CI: 0.53–0.93) were also observed. Conclusions: Beyond intrinsic risk factors, our results support associations of CM with multiple food groups and nutrients; if confirmed by prospective studies, these findings can add further knowledge about this fatal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma (CM) accounts for the majority of skin cancer-related deaths and, during recent decades, its incidence has increased worldwide. Although early-stage disease is associated with favourable prognosis, a subgroup of tumours is characterised by increased aggressiveness. High inter- and intra-tumour heterogeneity could contribute to the establishment of such aggressive phenotypes, which are based both on the genomic background and the transcriptomic plasticity of melanoma cells. Molecular profiling of melanomas has expanded our knowledge about mechanisms related to disease onset and progression, and it is key to improving optimal management. In this study, we aimed to characterise patients with primary CM for both germline and somatic variations as well as alterations at the gene expression level, by applying whole exome, targeted, and transcriptomic approaches and integrative, multi-layered bioinformatics analysis. Oncogenic alterations were identified, and distinct phenotypic cell states could be inferred from transcriptomic data. Cutaneous melanoma (CM) is the most aggressive type of skin cancer, and it is characterised by high mutational load and heterogeneity. In this study, we aimed to analyse the genomic and transcriptomic profile of primary melanomas from forty-six Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from Greek patients. Molecular analysis for both germline and somatic variations was performed in genomic DNA from peripheral blood and melanoma samples, respectively, exploiting whole exome and targeted sequencing, and transcriptomic analysis. Detailed clinicopathological data were also included in our analyses and previously reported associations with specific mutations were recognised. Most analysed samples (43/46) were found to harbour at least one clinically actionable somatic variant. A subset of samples was profiled at the transcriptomic level, and it was shown that specific melanoma phenotypic states could be inferred from bulk RNA isolated from FFPE primary melanoma tissue. Integrative bioinformatics analyses, including variant prioritisation, differential gene expression analysis, and functional and gene set enrichment analysis by group and per sample, were conducted and molecular circuits that are implicated in melanoma cell programmes were highlighted. Integration of mutational and transcriptomic data in CM characterisation could shed light on genes and pathways that support the maintenance of phenotypic states encrypted into heterogeneous primary tumours. [ABSTRACT FROM AUTHOR]

Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin-fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays after diagnostic examination, but isolated nucleic acids often suffer from degradation. Here, for the first time, we examine primary melanomas from Greek patients, using whole exome sequencing, so as to derive their mutational profile. Application of a bioinformatic framework revealed a total of 10,030 somatic mutations. Regarding the genes containing putative protein-altering mutations, 73 were common in at least three patients. Sixty-five of these 73 top common genes have been previously identified in melanoma cases. Biological processes related to melanoma were affected by varied genes in each patient, suggesting differences in the components of a pathway possibly contributing to pathogenesis. We performed a multi-level analysis highlighting a short list of candidate genes with a probable causative role in melanoma. [ABSTRACT FROM AUTHOR]