Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors

About 7% of all children's malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of simil...

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Autores: Pignata, Laura|||0000-0001-8835-5567, Palumbo, Orazio|||0000-0001-6583-3482, Cerrato, Flavia|||0000-0003-3794-3021, Acurzio, Basilia|||0000-0002-4703-8511, De Álava, Enrique|||0000-0001-8400-046X, Roma, Josep|||0000-0001-7692-6123, Gallego, Soledad|||0000-0002-4712-9624, Català-Mora, Jaume|||0000-0003-2152-8579, Carella, Massimo|||0000-0002-6830-6829, Riccio, Andrea|||0000-0001-7990-3576, Verde, Gaetano|||0000-0003-4768-0165
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253110
Acceso en línea:https://ddd.uab.cat/record/253110
https://dx.doi.org/urn:doi:10.3390/cancers12113411
Access Level:acceso abierto
Palabra clave:Nephroblastoma
Genomic imprinting
DNA methylation
Chromosome aberrations
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spelling Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms TumorsPignata, Laura|||0000-0001-8835-5567Palumbo, Orazio|||0000-0001-6583-3482Cerrato, Flavia|||0000-0003-3794-3021Acurzio, Basilia|||0000-0002-4703-8511De Álava, Enrique|||0000-0001-8400-046XRoma, Josep|||0000-0001-7692-6123Gallego, Soledad|||0000-0002-4712-9624Català-Mora, Jaume|||0000-0003-2152-8579Carella, Massimo|||0000-0002-6830-6829Riccio, Andrea|||0000-0001-7990-3576Verde, Gaetano|||0000-0003-4768-0165NephroblastomaGenomic imprintingDNA methylationChromosome aberrationsAbout 7% of all children's malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of similar alterations in pediatric malignancies. Our results demonstrated that 35% of WT cases were affected by methylation abnormalities of multiple imprinted loci. However, differently from adult cancers, they were associated with either chromosome aberrations or normal chromosome profiles. Epigenotype-phenotype correlations indicated that these epimutations were more frequent in highly aggressive tumors, suggesting the use of multiple methylation imprinting defects as a new informative marker for WT. The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children's malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is differentUniversitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/253110https://dx.doi.org/urn:doi:10.3390/cancers12113411reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2531102026-06-06T12:50:31Z
dc.title.none.fl_str_mv Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
title Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
spellingShingle Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
Pignata, Laura|||0000-0001-8835-5567
Nephroblastoma
Genomic imprinting
DNA methylation
Chromosome aberrations
title_short Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
title_full Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
title_fullStr Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
title_full_unstemmed Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
title_sort Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
dc.creator.none.fl_str_mv Pignata, Laura|||0000-0001-8835-5567
Palumbo, Orazio|||0000-0001-6583-3482
Cerrato, Flavia|||0000-0003-3794-3021
Acurzio, Basilia|||0000-0002-4703-8511
De Álava, Enrique|||0000-0001-8400-046X
Roma, Josep|||0000-0001-7692-6123
Gallego, Soledad|||0000-0002-4712-9624
Català-Mora, Jaume|||0000-0003-2152-8579
Carella, Massimo|||0000-0002-6830-6829
Riccio, Andrea|||0000-0001-7990-3576
Verde, Gaetano|||0000-0003-4768-0165
author Pignata, Laura|||0000-0001-8835-5567
author_facet Pignata, Laura|||0000-0001-8835-5567
Palumbo, Orazio|||0000-0001-6583-3482
Cerrato, Flavia|||0000-0003-3794-3021
Acurzio, Basilia|||0000-0002-4703-8511
De Álava, Enrique|||0000-0001-8400-046X
Roma, Josep|||0000-0001-7692-6123
Gallego, Soledad|||0000-0002-4712-9624
Català-Mora, Jaume|||0000-0003-2152-8579
Carella, Massimo|||0000-0002-6830-6829
Riccio, Andrea|||0000-0001-7990-3576
Verde, Gaetano|||0000-0003-4768-0165
author_role author
author2 Palumbo, Orazio|||0000-0001-6583-3482
Cerrato, Flavia|||0000-0003-3794-3021
Acurzio, Basilia|||0000-0002-4703-8511
De Álava, Enrique|||0000-0001-8400-046X
Roma, Josep|||0000-0001-7692-6123
Gallego, Soledad|||0000-0002-4712-9624
Català-Mora, Jaume|||0000-0003-2152-8579
Carella, Massimo|||0000-0002-6830-6829
Riccio, Andrea|||0000-0001-7990-3576
Verde, Gaetano|||0000-0003-4768-0165
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Nephroblastoma
Genomic imprinting
DNA methylation
Chromosome aberrations
topic Nephroblastoma
Genomic imprinting
DNA methylation
Chromosome aberrations
description About 7% of all children's malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of similar alterations in pediatric malignancies. Our results demonstrated that 35% of WT cases were affected by methylation abnormalities of multiple imprinted loci. However, differently from adult cancers, they were associated with either chromosome aberrations or normal chromosome profiles. Epigenotype-phenotype correlations indicated that these epimutations were more frequent in highly aggressive tumors, suggesting the use of multiple methylation imprinting defects as a new informative marker for WT. The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children's malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/253110
https://dx.doi.org/urn:doi:10.3390/cancers12113411
url https://ddd.uab.cat/record/253110
https://dx.doi.org/urn:doi:10.3390/cancers12113411
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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