Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib.
Pigment Cell Melanoma Res
; 28(3): 318-23, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25515853
ABSTRACT
Resistance to treatment is the main problem of targeted treatment for cancer. We followed ten patients during treatment with vemurafenib, by three-dimensional imaging. In all patients, only a subset of lesions progressed. Next-generation DNA sequencing was performed on sequential biopsies in four patients to uncover mechanisms of resistance. In two patients, we identified mutations that explained resistance to vemurafenib; one of these patients had a secondary BRAF L505H mutation. This is the first observation of a secondary BRAF mutation in a vemurafenib-resistant patient-derived melanoma sample, which confirms the potential importance of the BRAF L505H mutation in the development of therapy resistance. Moreover, this study hints toward an important role for tumor heterogeneity in determining the outcome of targeted treatments.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Sulfonamidas
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Diagnóstico por Imagen
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Heterogeneidad Genética
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Resistencia a Antineoplásicos
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Proteínas Proto-Oncogénicas B-raf
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Indoles
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Melanoma
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Mutación
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Países Bajos