Next-generation sequencing in the identification of biomarkers in cutaneous melanoma according to the etiopathogenic development pathway and their potential clinical relevance

• Autores: David Millán Esteban
• Directores de la Tesis: Zaida García Casado (dir. tes.), Eduardo Nagore Enguídanos (dir. tes.), María Belén Pico Sirvent (tut. tes.)
• Lectura: En la Universitat Politècnica de València ( España ) en 2022
• Idioma: español
• Tribunal Calificador de la Tesis: Irene Orlow (presid.), Eloisa Jantus Lewintre (secret.), Ana Lluch Hernández (voc.)
• Programa de doctorado: Programa de Doctorado en Biotecnología por la Universitat Politècnica de València
• Materias:
  • Ciencias de la vida
    • Biología humana
      • Genética humana
    • Biología molecular
    • Biología vegetal (botánica)
  • Ciencias médicas
    • Ciencias clínicas
      • Dermatología
    • Patología
      • Oncología
• Enlaces
  • Tesis en acceso abierto en: RiuNet
• Resumen

  • Melanoma is the deadliest and most dangerous type of skin cancer, given that a small tumor can spread and result in metastasis. Over the years, classifications have been made either from a clinical, epidemiological or molecular point of view. Current classifications use the degree of solar exposure and tumoral location to divide into different melanoma groups.

    In 1998, David Whiteman and collaborators proposed the divergent pathway model for melanoma development. This presented two pathways to melanomagenesis: one related to melanocytic proliferation (nevogenic) and the other related to chronic sun exposure (CSD). Despite corroborations of this model from the clinic and epidemiology, it is yet to be molecularly characterized in depth.

    At a general level, different genes had been identified with relevant mutations for the development of melanoma, as is the gene KIT. However, there was a lack of knowledge on how these mutations were distributed among different melanoma subgroups, as well as the potential prognostic value.

    In this thesis we have implemented sequencing techniques - both massive and traditional - to characterize the mutational profile of the two populations proposed by the divergent pathways model. We found differences both in the number of mutations and in the genes carrying the mutations. We have also seen how melanomas harboring KIT mutations seem to develop in a way which is independent from the known etiology, and how the mutational status of this gene lacks prognostic value on the outcome of the patients.