RT Journal Article
T1 Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development
A1 Millan-Esteban, David
A1 Pena-Chilet, Maria
A1 Garcia-Casado, Zaida
A1 Manrique-Silva, Esperanza
A1 Requena, Celia
A1 Banuls, Jose
A1 Lopez-Guerrero, Jose Antonio
A1 Rodriguez-Hernandez, Aranzazu
A1 Traves, Victor
A1 Dopazo, Joaquin
A1 Viros, Amaya
A1 Kumar, Rajiv
A1 Nagore, Eduardo
K1 melanoma
K1 etiopathogeny
K1 mutations
K1 Tert promoter mutations
K1 Melanocytic nevi
K1 Therapeutic targets
K1 Solar keratoses
K1 Braf mutations
K1 Cancer
K1 Risk
K1 Classification
K1 Skin
AB Simple SummaryThe 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.
PB Mdpi
YR 2021
FD 2021-10-01
LK https://hdl.handle.net/10668/24619
UL https://hdl.handle.net/10668/24619
LA en
DS RISalud
RD Apr 6, 2025