RESUMEN

BACKGROUND: SMARCB1 (INI1/BAF47/SNF5) encodes a part of a multiprotein complex that regulates gene expression through chromatin remodeling. SMARCB1 expression is lost or downregulated in multiple human tumors, including epithelioid sarcoma, meningioma and rhabdoid tumors of the brain, soft tissue and kidney. METHODS: A 46-gene or 50-gene next-generation sequencing AmpliSeq Cancer Panel (Life Technologies; San Francisco, CA, USA) was applied to ∼1400 primary or metastatic melanoma tissues. RESULTS: We identified eight cases of melanoma harboring mutations in SMARCB1. Immunohistochemistry demonstrated preservation of SMARCB1 protein expression in all cases. SMARCB1 mutations occurred together with TP53 mutations in five of the eight cases, suggesting a functional relationship between these tumor suppressors in melanoma. CONCLUSIONS: Because single-base substitutions in SMARCB1 occur in a small subset of melanomas and do not affect SMARCB1 protein expression, such mutations would only be discovered by sequencing approaches. Our findings highlight the potential for next-generation sequencing platforms to identify mutations unexpected for melanoma that may contribute to its oncogenic potential. Though rare, the identification of SMARCB1 mutations adds to the growing literature regarding the role of epigenetic control mechanisms in melanoma progression and therapeutic resistance and provide a rationale for strategies targeting such alterations (via chromatin remodeling agents) in clinical trials.

Asunto(s)

Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Melanoma/genética , Mutación , Análisis de Secuencia de ADN/métodos , Factores de Transcripción/genética , Adulto , Anciano , Anciano de 80 o más Años , Regulación hacia Abajo , Epigénesis Genética , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Proteína SMARCB1 , Proteína p53 Supresora de Tumor/genética