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LINE-1 hypomethylation and mutational status in cutaneous melanomas.
Pramio, Dimitrius T; Pennacchi, Paula C; Maria-Engler, Silvya S; Campos, Antônio H J F M; Duprat, João P; Carraro, Dirce M; Krepischi, Ana C V.
Afiliación
  • Pramio DT; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
  • Pennacchi PC; Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
  • Maria-Engler SS; Clinical Chemistry and Toxicology Department, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
  • Campos AH; Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil.
  • Duprat JP; Skin Cancer Department, AC Camargo Cancer Center, São Paulo, Brazil.
  • Carraro DM; International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
  • Krepischi AC; Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
J Investig Med ; 64(4): 899-904, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26965315
Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. In this work, LINE-1 methylation levels were evaluated in cutaneous melanomas and normal melanocyte primary cell cultures to investigate their possible association with both distinct clinicopathological characteristics and tumor mutational profile. A set of driver mutations frequently identified in cutaneous melanoma was assessed by sequencing (actionable mutations in BRAF, NRAS, and KIT genes, and mutations affecting the TER T promoter) or multiplex ligation-dependent probe amplification (MLPA) (CDKN2A deletions). Pyrosequencing was performed to investigate the methylation level of LINE-1 and CDKN2A promoter sequences. The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (>4 mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Elementos de Nucleótido Esparcido Largo / Melanoma / Mutación Tipo de estudio: Prognostic_studies / Qualitative_research Límite: Humans Idioma: En Revista: J Investig Med Asunto de la revista: MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilación de ADN / Elementos de Nucleótido Esparcido Largo / Melanoma / Mutación Tipo de estudio: Prognostic_studies / Qualitative_research Límite: Humans Idioma: En Revista: J Investig Med Asunto de la revista: MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido