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

ABSTRACT: Ultraviolet radiation (UV) is causally linked to cutaneous melanoma, yet the underlying epigenetic mechanisms, known as molecular sensors of exposure, have never been characterized in clinical biospecimen. DNA methylome, genome and transcriptome analyses of cutaneous melanoma in two cohorts identified UV-related alterations in regulatory regions and immunological pathways and revealed novel cancer driver genes affecting patient survival. TAPBP, the top gene and a member of the immunoglobulin superfamily, encompassed several CpG methylation sites altered by UV and independently validated by bisulfite pyrosequencing, providing cost-effective opportunities for clinical application. The DNA methylome also highlighted non UV-related aberrations underlying pathological differences between cutaneous and 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 in multi-ethnic backgrounds reveal translationally impactful mechanisms in melanomagenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE202750 | GEO | 2022/05/12

REPOSITORIES: GEO