Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure.
Anna Luiza Silva Almeida VicenteAlexei NovoloacaVincent CahaisZainab AwadaCyrille CueninNatália SpitzAndré Lopes CarvalhoAdriane Feijó EvangelistaCamila Souza CrovadorRui Manuel Vieira ReisZdenko HercegVinicius de Lima VazquezAkram GhantousPublished in: Nature communications (2022)
Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have not been characterized in clinical biospecimens. Here, we integrate clinical, epigenome (DNA methylome), genome and transcriptome profiling of 112 cutaneous melanoma from two multi-ethnic cohorts. We identify UV-related alterations in regulatory regions and immunological pathways, with multi-OMICs cancer driver potential affecting patient survival. TAPBP, the top gene, is critically involved in immune function and encompasses several UV-altered methylation sites that were validated by targeted sequencing, providing cost-effective opportunities for clinical application. The DNA methylome also reveals non UV-related aberrations underlying pathological differences between the cutaneous and 17 acral melanomas. Unsupervised epigenomic mapping demonstrated that non UV-mutant cutaneous melanoma more closely resembles acral rather than UV-exposed cutaneous melanoma, with the latter showing better patient prognosis than the other two forms. These gene-environment interactions reveal translationally impactful mechanisms in melanomagenesis.
Keyphrases
- single cell
- genome wide
- dna methylation
- skin cancer
- copy number
- papillary thyroid
- rna seq
- gene expression
- single molecule
- case report
- machine learning
- high resolution
- squamous cell
- squamous cell carcinoma
- basal cell carcinoma
- radiation therapy
- transcription factor
- young adults
- climate change
- drug delivery
- genome wide identification
- cancer therapy
- lymph node metastasis
- drug induced