Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development
Por:
Millan-Esteban, D, Pena-Chilet, M, Garcia-Casado, Z, Manrique-Silva, E, Requena, C, Banuls, J, Lopez-Guerrero, J, Rodriguez-Hernandez, A, Traves, V, Dopazo, J, Viros, A, Kumar, R and Nagore, E
Publicada:
1 oct 2021
Ahead of Print:
18 oct 2021
Resumen:
Simple Summary
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.
Filiaciones:
Millan-Esteban, D:
Univ Catolica Valencia San Vicente Martir, Sch Med, Valencia 46001, Spain
Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain
Pena-Chilet, M:
Hosp Virgen Rocio, Fdn Progreso & Salud, Clin Bioinformat Area, Seville 41013, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Bioinformat Rare Dis BiER, Seville 41013, Spain
Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain
Garcia-Casado, Z:
Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain
Manrique-Silva, E:
Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain
Requena, C:
Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain
:
Hosp Gen Univ Alicante, El Inst Invest Sanitari & Biomed Alicante ISABIAL, Dept Dermatol, Alicante 03010, Spain
Lopez-Guerrero, J:
Fdn Inst Valenciano Onco, Mol Biol Lab, Valencia 46009, Spain
Rodriguez-Hernandez, A:
Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain
Traves, V:
Fdn Inst Valenciano Oncol, Dept Pathol Anat, Valencia 46009, Spain
Dopazo, J:
Hosp Virgen Rocio, Fdn Progreso & Salud, Clin Bioinformat Area, Seville 41013, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Bioinformat Rare Dis BiER, Seville 41013, Spain
Hosp Virgen Rocio, Inst Biomed Seville IBIS, Computat Syst Med, Seville 41013, Spain
Hosp Virgen Rocio, Fdn Progreso & Salud ELIXIRes, Seville 41013, Spain
Viros, A:
Univ Manchester, Canc Res UK Manchester Inst, Skin Canc & Aging Lab, Manchester SK10 4TG, Lancs, England
Kumar, R:
Deutsch Krebsforschungzentrum, Div Funct Genome Anal, D-69120 Heidelberg, Germany
Czech Acad Sci, Inst Expt Med, Dept Mol Biol Canc, Prague 14220, Czech Republic
Heidelberg Univ, Inst Med Biometry & Informat, D-69117 Heidelberg, Germany
Nagore, E:
Univ Catolica Valencia San Vicente Martir, Sch Med, Valencia 46001, Spain
Fdn Inst Valenciano Oncol, Dept Dermatol, Valencia 46009, Spain
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