Cutaneous and acral melanoma cross-OMICs reveals prognostic cancer drivers associated with pathobiology and ultraviolet exposure

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Almeida Vicente, Anna Luiza Silva ; Novoloaca, Alexei ; Cahais, Vincent ; Awada, Zainab ; Cuenin, Cyrille ; Spitz, Natalia ; Carvalho, Andre Lopes ; Evangelista, Adriane Feijo ; Crovador, Camila Souza ; Reis, Rui Manuel ; Herceg, Zdenko ; Vazquez, Vinicius de Lima ; Ghantous, Akram

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 15-pg., 2022-07-15.

Abstract

While cutaneous melanoma is linked to UV radiation, acral melanoma is not. Epigenetic mechanisms function as sensors to exposures and determinants of cell identity. Here, the authors use DNA methylation data to identify dysregulated pathways associated with UV radiation and pathobiology in cutaneous and acral melanomas. 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. (AU)

• FAPESP's process: 16/15941-3 - The Role of Methylation in the Melanoma Initiation and Progression and the Epigenetic Impact in vitro
• Grantee: Anna Luiza Silva Almeida Vicente
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/09612-0 - The Role of Methylation in the Melanoma Initiation and Progression and the Epigenetic Impact in vitro
• Grantee: Anna Luiza Silva Almeida Vicente
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate