Copy number rather than epigenetic alterations are the major dictator of imprinted methylation in tumors

It has been postulated that imprinting aberrations are common in tumors. To understand the role of imprinting in cancer, we have characterized copy-number and methylation in over 280 cancer cell lines and confirm our observations in primary tumors. Imprinted differentially methylated regions (DMRs)...

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Detalles Bibliográficos
Autores: Martín Trujillo, Alex, Vidal, Enrique, Monteagudo Sánchez, Ana, Sánchez Delgado, Marta, Moran, Sebastian, Hernandez Mora, Jose Ramon, Heyn, Holger, Guitart, Miriam, Esteller, Manel, Monk, David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/122164
Acceso en línea:https://hdl.handle.net/2445/122164
Access Level:acceso abierto
Palabra clave:Variació en el nombre de còpies
Epigenètica
Metilació
Tumors
Càncer
Copy number variation
Epigenetics
Methylation
Cancer
Descripción
Sumario:It has been postulated that imprinting aberrations are common in tumors. To understand the role of imprinting in cancer, we have characterized copy-number and methylation in over 280 cancer cell lines and confirm our observations in primary tumors. Imprinted differentially methylated regions (DMRs) regulate parent-of-origin monoallelic expression of neighboring transcripts in cis. Unlike single-copy CpG islands that may be prone to hypermethylation, imprinted DMRs can either loose or gain methylation during tumorigenesis. Here, we show that methylation profiles at imprinted DMRs often not represent genuine epigenetic changes but simply the accumulation of underlying copy-number aberrations (CNAs), which is independent of the genome methylation state inferred from cancer susceptible loci. Our results reveal that CNAs also influence allelic expression as loci with copy-number neutral loss-of-heterozygosity or amplifications may be expressed from the appropriate parental chromosomes, which is indicative of maintained imprinting, although not observed as a single expression foci by RNA FISH.