RESUMEN

Inorganic arsenic is a well-known carcinogen associated with several types of cancer, but the mechanisms involved in arsenic-induced carcinogenesis are not fully understood. Recent evidence points to epigenetic dysregulation as an important mechanism in this process; however, the effects of epigenetic alterations in gene expression have not been explored in depth. Using microarray data and applying a multivariate clustering analysis in a Gaussian mixture model, we describe the alterations in DNA methylation around the promoter region and the impact on gene expression in HaCaT cells during the transformation process caused by chronic exposure to arsenic. Using this clustering approach, the genes were grouped according to their methylation and expression status in the epigenetic landscape, and the changes that occurred during the cellular transformation were identified adequately. Thus, we present a valuable method for identifying epigenomic dysregulation.

Asunto(s)

Arsénico/toxicidad , Transformación Celular Neoplásica/patología , Metilación de ADN/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Neoplasias Cutáneas/patología , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/genética , Epigénesis Genética/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Trasplante de Neoplasias , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/genética