A Comprehensive Analysis of Cutaneous Melanoma Patients in Greece Based on Multi-Omic Data.
Georgia KontogianniKonstantinos VoutetakisGeorgia PirotiKaterina KypreouIrene StefanakiEfstathios Iason VlachavasEleftherios PilalisAlexander StratigosAristotelis ChatziioannouOlga PapadodimaPublished in: Cancers (2023)
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.
Keyphrases
- skin cancer
- single cell
- copy number
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- peripheral blood
- genome wide
- electronic health record
- rna seq
- genome wide identification
- big data
- peritoneal dialysis
- dna methylation
- stem cells
- basal cell carcinoma
- single molecule
- drug delivery
- bone marrow
- dna repair
- machine learning
- transcription factor
- cell free
- circulating tumor cells