Epigenetic signature of differentially methylated genes in cutaneous melanoma
Appl. cancer res
; 37: 1-5, 2017. tab, ilus
Artigo
em Inglês
| LILACS, Inca
| ID: biblio-914894
Biblioteca responsável:
BR30.1
ABSTRACT
Background:
Cutaneous melanoma (CM) is the most aggressive subtype of skin cancer, with increasing incidence over the past several decades. DNA methylation is a key element of several biological processes such as genomic imprinting, cell differentiation and senescence, and deregulation of this mechanism has been implicated in several diseases, including cancer. In order to understand the relationship of DNA methylation in CMs, we searched for an epigenetic signature of cutaneous melanomas by comparing the DNA methylation profiles between tumours and benign melanocytes, the precursor cells of CM.Methods:
We used 20 primary CMs and three primary cell cultures of melanocytes as a discovery cohort. The tumours mutational background was collected as previously reported. Methylomes were obtained using the HM450K DNA methylation assay, and differential methylation analysis was performed. DNA methylation data of CMs from TCGA were recovered to validate our findings.Results:
A signature of 514 differentially methylated genes (DMGs) was evident in CMs compared to melanocytes, which was independent of the presence of driver mutations. Pathway analysis of this CM signature revealed an enrichment of proteins involved in the binding of DNA regulatory regions (hypermethylated sites), and related to transmembrane signal transducer activities (hypomethylated sites). The methylation signature was validated in an independent dataset of primary CMs, as well as in lymph node and distant metastases (correlation of DNA methylation level r > 0,95; Pearson's test p < 2.2e-16).Conclusions:
CMs exhibited a DMGs signature, which was independent of the mutational background and possibly established prior to genetic alterations. This signature provides important insights into how epigenetic deregulation contributes to melanomagenesis in general (AU)
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
/
Inca
Assunto principal:
Neoplasias Cutâneas
/
Transdução de Sinais
/
Metilação de DNA
/
Proteínas de Ligação a DNA
/
Transcriptoma
/
Melanoma
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Appl. cancer res
Assunto da revista:
Neoplasias
Ano de publicação:
2017
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
A.C.Camargo Cancer Center/BR
/
Universidade Tecnológica Federal do Paraná/BR
/
University of São Paulo/BR