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

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  • dc.contributor.author Martin-Trujillo, Alexca
  • dc.contributor.author Vidal Ocabo, Enriqueca
  • dc.contributor.author Monteagudo-Sánchez, Anaca
  • dc.contributor.author Sanchez-Delgado, Martaca
  • dc.contributor.author Moran, Sebastianca
  • dc.contributor.author Hernández Mora, José Ramónca
  • dc.contributor.author Heyn, Holgerca
  • dc.contributor.author Guitart, Miriamca
  • dc.contributor.author Esteller, Manelca
  • dc.contributor.author Monk, Davidca
  • dc.date.accessioned 2018-06-20T07:15:59Z
  • dc.date.available 2018-06-20T07:15:59Z
  • dc.date.issued 2017
  • dc.description.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.Altered genomic imprinting is frequently reported in cancer. Here, the authors analyze copy number and methylation in cancer cell lines and primary tumors to show that imprinted methylation profiles represent the accumulation of copy number alteration, rather than epigenetic alterations.
  • dc.description.sponsorship This work was supported by Spanish Ministerio de Educación y Competitividad (MINECO) (BFU2011-27658 and BFU2014-53093-R to D.M.), co-financed by the European Regional Development Fund (FEDER), the Asociaciòn Española Contra el Cáncer (AECC to D.M.) and the Fundaciò Olga Torres (FOT to H.H.). AMS is a recipient of a FPI PhD studentship from MINECO (BFU2014-53093) and H.H. is a Miguel Servet (CP14/00229) researcher funded by the Spanish Institute of Health Carlos III (ISCIII). Work supported by the Xarxa de Bancs de Tumors de Catalunya is sponsored by Pla Director d'Oncologia de Catalunya (XBTC).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Martin-Trujillo A, Vidal E, Monteagudo-Sánchez A, Sanchez-Delgado M, Moran S, Hernandez Mora JR et al. Copy number rather than epigenetic alterations are the major dictator of imprinted methylation in tumors. Nat Commun. 2017 Sep 7;8(1):467. DOI: 10.1038/s41467-017-00639-9
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-017-00639-9
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/34939
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Nature Communications. 2017 Sep 7;8(1):467
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-27658
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-53093-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-53093
  • dc.rights © The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cancer genomics
  • dc.subject.keyword Imprinting
  • dc.title Copy number rather than epigenetic alterations are the major dictator of imprinted methylation in tumorsca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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