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

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Martin-Trujillo, Alex, Vidal, Enrique, Monteagudo-Sánchez, Ana, Sanchez-Delgado, Marta, Moran, Sebastian, Hernandez Mora, Jose Ramon, Heyn, Holger, Guitart, Miriam, Esteller, Manel and Monk, David (2017) Copy number rather than epigenetic alterations are the major dictator of imprinted methylation in tumors. Nature Communications, 8 (1). ISSN 2041-1723

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 10 Nov 2020 01:18
Last Modified: 22 Oct 2022 07:26
URI: https://ueaeprints.uea.ac.uk/id/eprint/77615
DOI: 10.1038/s41467-017-00639-9

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