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Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

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    0560675 - ÚEM 2023 RIV CH eng J - Journal Article
    Millan-Esteban, D. - Pena-Chilet, M. - Garcia-Casado, Z. - Manrique-Silva, E. - Requena, C. - Banuls, J. - Lopez-Guerrero, J.A. - Rodriguez-Hernandez, A. - Traves, V. - Dopazo, J. - Viróz, A. - Kunar, Rajiv - Nagore, E.
    Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development.
    Cancers (Basel). Roč. 13, č. 20 (2021), č. článku 5219. E-ISSN 2072-6694
    Institutional support: RVO:68378041
    Keywords : melanoma * etiopathogeny * mutations
    OECD category: Genetics and heredity (medical genetics to be 3)
    Impact factor: 6.575, year: 2021
    Method of publishing: Open access
    https://www.mdpi.com/2072-6694/13/20/5219

    The divergent pathway model established at least two approaches for melanoma development. One was related to a propensity to melanocytic proliferation (nevogenic), and the other was associated with an accumulation of solar damage (CSD). We conducted a retrospective study to examine whether this model had a molecular support using sequencing and bioinformatic tools on a set of cutaneous melanomas corresponding to these two groups. We found that the nevogenic melanomas were associated with mutations in BRAF, while the CSD melanomas were associated with mutations in NF1, ROS1, GNA11, and RAC1. We concluded that nevogenic and CSD melanomas constitute two different biological entities.
    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.
    Permanent Link: https://hdl.handle.net/11104/0333536

     
     
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