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

Anna Luiza Silva Almeida Vicente (), Alexei Novoloaca, Vincent Cahais, Zainab Awada, Cyrille Cuenin, Natália Spitz, André Lopes Carvalho, Adriane Feijó Evangelista, Camila Souza Crovador, Rui Manuel Reis, Zdenko Herceg, Vinicius Lima Vazquez and Akram Ghantous ()
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Anna Luiza Silva Almeida Vicente: Barretos Cancer Hospital
Alexei Novoloaca: International Agency for Research on Cancer (IARC)
Vincent Cahais: International Agency for Research on Cancer (IARC)
Zainab Awada: International Agency for Research on Cancer (IARC)
Cyrille Cuenin: International Agency for Research on Cancer (IARC)
Natália Spitz: International Agency for Research on Cancer (IARC)
André Lopes Carvalho: Barretos Cancer Hospital
Adriane Feijó Evangelista: Barretos Cancer Hospital
Camila Souza Crovador: Barretos Cancer Hospital
Rui Manuel Reis: Barretos Cancer Hospital
Zdenko Herceg: International Agency for Research on Cancer (IARC)
Vinicius Lima Vazquez: Barretos Cancer Hospital
Akram Ghantous: International Agency for Research on Cancer (IARC)

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31488-w

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