According to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies.

Bioinformatics in Rare Diseases 41013 Sevilla Spain

Clinical Bioinformatics Area Fundación Progreso y Salud Hospital Virgen del Rocío 41013 Sevilla Spain

Computational Systems Medicine Institute of Biomedicine of Seville Hospital Virgen del Rocío 41013 Sevilla Spain

Department of Dermatology El Instituto de Investigación Sanitaria y Biomédica de Alicante Hospital General Universitario de Alicante 03010 Alicante Spain

Department of Dermatology Fundación Instituto Valenciano de Oncología 46009 Valencia Spain

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 142 20 Prague Czech Republic

Department of Pathological Anatomy Fundación Instituto Valenciano de Oncología 46009 Valencia Spain

Division of Functional Genome Analysis Deutsches Krebsforschüngzentrum 69120 Heidelberg Germany

Fundación Progreso y Salud ELIXIR es Hospital Virgen del Rocío 41013 Sevilla Spain

Institute of Medical Biometry and Informatics University of Heidelberg 69117 Heidelberg Germany

Laboratory of Molecular Biology Fundación Instituto Valenciano de Oncología 46009 Valencia Spain

School of Medicine Universidad Católica de València San Vicente Mártir 46001 Valencia Spain

Skin Cancer and Aging Lab Cancer Research UK Manchester Institute University of Manchester Manchester SK10 4TG UK

Zobrazit více v PubMed

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